Cystic fibrosis and defective airway innate immunity

Antimicrobial Peptides and Innate Immunity

Volumn , Issue , 2013, Pages 275-306

  Bartlett, Jennifer A ^a   McCray, Paul B ^a  

^a UNIVERSITY OF IOWA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84901622801     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-3-0348-0541-4_11     Document Type: Chapter

References (249)

1. Abman SH, Ogle JW, Butler-Simon N, Rumack CM, Accurso FJ (1988) Role of respiratory syncytial virus in early hospitalizations for respiratory distress of young infants with cystic fibrosis. J Pediatr 113(5):826-830
2. Agerberth B, Charo J, Werr J, Olsson B, Idali F, Lindbom L, Kiessling R, Jornvall H, Wigzell H, Gudmundsson GH (2000) The human antimicrobial and chemotactic peptides LL-37 and alpha-defensins are expressed by specific lymphocyte and monocyte populations. Blood 96(9):3086-3093
3. Akira S, Takeda K (2004) Toll-like receptor signalling. Nat Rev Immunol 4(7):499-511
4. Andersen DH (1938) Cystic fibrosis of the pancreas and its relation to celiac disease: a clinical and pathological study. Am J Dis Child 56:344-399
5. Anderson MP, Gregory RJ, Thompson S, Souza DW, Paul S, Mulligan RC, Smith AE, Welsh MJ (1991a) Demonstration that CFTR is a chloride channel by alteration of its anion selectivity. Science 253:202-205
6. Anderson MP, Rich DP, Gregory RJ, Smith AE, Welsh MJ (1991b) Generation of cAMP-activated chloride currents by expression of CFTR. Science 251(4994):679-682
7. Andrejeva J, Childs KS, Young DF, Carlos TS, Stock N, Goodbourn S, Randall RE (2004) The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN-beta promoter. Proc Natl Acad Sci USA 101(49):17264-17269
8. Andresen E, Lange C, Strodthoff D, Goldmann T, Fischer N, Sahly H, Branscheid D, Heine H (2011) S100A7/psoriasin expression in the human lung: unchanged in patients with COPD, but upregulated upon positive S. aureus detection. BMC Pulm Med 11:10
9. Armstrong DS, Hook SM, Jamsen KM, Nixon GM, Carzino R, Carlin JB, Robertson CF, Grimwood K (2005) Lower airway inflammation in infants with cystic fibrosis detected by newborn screening. Pediatr Pulmonol 40(6):500-510
10. Arnold RR, Brewer M, Gauthier JJ (1980) Bactericidal activity of human lactoferrin: sensitivity of a variety of microorganisms. Infect Immun 28(3):893-898
11. Aron Y, Polla BS, Bienvenu T, Dall'ava J, Dusser D, Hubert D (1999) HLA class II polymorphism in cystic fibrosis. A possible modifier of pulmonary phenotype. Am J Respir Crit Care Med 159(5 Pt 1):1464-1468
12. Balough K, McCubbin M, Weinberger M, Smits W, Ahrens R, Fick R (1995) The relationship between infection and inflammation in the early stages of lung disease from cystic fibrosis. Pediatr Pulmonol 20(2):63-70
13. Bals R, Wang X, Wu Z, Freeman T, Bafna V, Zasloff M, Wilson JM (1998a) Human beta-defensin 2 is a salt-sensitive peptide antibiotic expressed in human lung. J Clin Invest 102(5):874-880
14. Bals R, Wang X, Zasloff M, Wilson JM (1998b) The peptide antibiotic LL-37/hCAP-18 is expressed in epithelia of the human lung where it has broad antimicrobial activity at the airway surface. Proc Natl Acad Sci USA 95(16):9541-9546
15. Bartlett JA, Fischer AJ, McCray PB Jr (2008a) Innate immune functions of the airway epithelium. Contrib Microbiol 15:147-163
16. Bartlett JA, Hicks BJ, Schlomann JM, Ramachandran S, Nauseef WM, McCray PB Jr (2008b) PLUNC is a secreted product of neutrophil granules. J Leukoc Biol 83(5):1201-1206
17. Bedrossian CW, Greenberg SD, Singer DB, Hansen JJ, Rosenberg HS (1976) The lung in cystic fibrosis. A quantitative study including prevalence of pathologic findings among different age groups. Hum Pathol 7(2): 195-204
18. Bhaskar KR, Gong DH, Bansil R, Pajevic S, Hamilton JA, Turner BS, LaMont JT (1991) Profound increase in viscosity and aggregation of pig gastric mucin at low pH. Am J Physiol 261(5 Pt 1): G827-G832
19. Bingle CD, Bingle L (2000) Characterisation of the human plunc gene, a gene product with an upper airways and nasopharyngeal restricted expression pattern. Biochim Biophys Acta 1493(3):363-367
20. Bjamsholt T, Jensen PO, Fiandaca MJ, Pedersen J, Hansen CR, Andersen CB, Pressler T, Givskov M, Hoiby N (2009) Pseudomonas aeruginosa biofilms in the respiratory tract of cystic fibrosis patients. Pediatr Pulmonol 44(6):547-558
21. Boucher RC (2004) New concepts of the pathogenesis of cystic fibrosis lung disease. Eur Respir J 23(1):146-158
22. Boucher RC (2007) Evidence for airway surface dehydration as the initiating event in CF airway disease. J Intern Med 261(1):5-16
23. Britigan BE, Hayek MB, Doebbeling BN, Fick RB Jr (1993) Transferrin and lactoferrin undergo proteolytic cleavage in the Pseudomonas aeruginosa-infected lungs of patients with cystic fibrosis. Infect Immun 61(12):5049-5055
24. Bubien JK (2001) CFTR may play a role in regulated secretion by lymphocytes: a new hypothesis for the pathophysiology of cystic fibrosis. Pflugers Arch 443(Suppl 1):S36-S39
25. Bubien JK, Kirk KL, Rado TA, Frizzell RA (1990) Cell cycle dependence of chloride permeability in normal and cystic fibrosis lymphocytes. Science 248(4961):1416-1419
26. Butler MW, Robertson I, Greene CM, O'Neill SJ, Taggart CC, McElvaney NG (2006) Elafin prevents lipopolysaccharide-induced AP-1 and NF-kappaB activation via an effect on the ubiquitin-proteasome pathway. J Biol Chem 281(46):34730-34735
27. Caldwell RA, Grubb BR, Tarran R, Boucher RC, Knowles MR, Barker PM (2002) In vivo airway surface liquid Cl- analysis with solid-state electrodes. J Gen Physiol 119(1):3-14
28. Candiano G, Bruschi M, Pedemonte N, Musante L, Ravazzolo R, Liberatori S, Bini L, Galietta LJ, Zegarra-Moran O (2007) Proteomic analysis of the airway surface liquid: modulation by proinflammatory cytokines. Am J Physiol Lung Cell Mol Physiol 292(1):L185-L198
29. Cassel SL, Sutterwala FS (2010) Sterile inflammatory responses mediated by the NLRP3 inflammasome. Eur J Immunol 40(3):607-611
30. Chen EY, Yang N, Quinton PM, Chin WC (2010a) A new role for bicarbonate in mucus formation. Am J Physiol Lung Cell Mol Physiol 299(4):L542-L549
31. Chen JH, Stoltz DA, Karp PH, Ernst SE, Pezzulo AA, Moninger TO, Rector MV, Reznikov LR, Launspach JL, Chaloner K, Zabner J, Welsh MJ (2010b) Loss of anion transport without increased sodium absorption characterizes newborn porcine cystic fibrosis airway epithelia. Cell 143(6):911-923
32. Chertov O, Michiel DF, Xu L, Wang JM, Tani K, Murphy WJ, Longo DL, Taub DD, Oppenheim JJ (1996) Identification of defensin-1, defensin-2, and CAP37/azurocidin as T-cell chemoattractant proteins released from interleukin-8-stimulated neutrophils. J Biol Chem 271(6):2935-2940
33. Choi JY, Joo NS, Krouse ME, Wu JV, Robbins RC, Ianowski JP, Hanrahan JW, Wine JJ (2007) Synergistic airway gland mucus secretion in response to vasoactive intestinal peptide and carbachol is lost in cystic fibrosis. J Clin Invest 117(10):3118-3127
34. Choi JY, Khansaheb M, Joo NS, Krouse ME, Robbins RC, Weill D, Wine JJ (2009) Substance P stimulates human airway submucosal gland secretion mainly via a CFTR-dependent process. J Clin Invest 119(5):1189-1200
35. Chu HW, Thaikoottathil J, Rino JG, Zhang G, Wu Q, Moss T, Refaeli Y, Bowler R, Wenzel SE, Chen Z, Zdunek J, Breed R, Young R, Allaire E, Martin RJ (2007) Function and regulation of SPLUNC1 protein in Mycoplasma infection and allergic inflammation. J Immunol 179(6):3995-4002
36. Clary-Meinesz C, Mouroux J, Cosson J, Huitorel P, Blaive B (1998) Influence of external pH on ciliary beat frequency in human bronchi and bronchioles. Eur Respir J 11(2):330-333
37. Coakley RD, Boucher RC (2001) Regulation and functional significance of airway surface liquid pH. JOP 2(4 Suppl):294-300
38. Coakley RD, Grubb BR, Paradiso AM, Gatzy JT, Johnson LG, Kreda SM, O'Neal WK, Boucher RC (2003) Abnormal surface liquid pH regulation by cultured cystic fibrosis bronchial epithelium. Proc Natl Acad Sci USA 100(26):16083-16088
39. Cole AM, Dewan P, Ganz T (1999) Innate antimicrobial activity of nasal secretions. Infect Immun 67(7):3267-3275
40. Cole AM, Kim YH, Tahk S, Hong T, Weis P, Waring AJ, Ganz T (2001) Calcitermin, a novel antimicrobial peptide isolated from human airway secretions. FEBS Lett 504(1-2):5-10
41. Cole AM, Liao HI, Stuchlik O, Tilan J, Pohl J, Ganz T (2002) Cationic polypeptides are required for antibacterial activity of human airway fluid. J Immunol 169(12):6985-6991
42. Conner GE, Salathe M, Forteza R (2002) Lactoperoxidase and hydrogen peroxide metabolism in the airway. Am J Respir Crit Care Med 166(12 Pt 2):S57-S61
43. Conner GE, Wijkstrom-Frei C, Randell SH, Fernandez VE, Salathe M (2007) The lactoperoxidase system links anion transport to host defense in cystic fibrosis. FEBS Lett 581(2):271-278
44. Corbin BD, Seeley EH, Raab A, Feldmann J, Miller MR, Torres VJ, Anderson KL, Dattilo BM, Dunman PM, Gerads R, Caprioli RM, Nacken W, Chazin WJ, Skaar EP (2008) Metal chelation and inhibition of bacterial growth in tissue abscesses. Science 319(5865):962-965
45. Cornish CJ, Devery JM, Poronnik P, Lackmann M, Cook DI, Geczy CL (1996) S100 protein CP-10 stimulates myeloid cell chemotaxis without activation. J Cell Physiol 166(2):427-437
46. Cowland JB, Johnsen AH, Borregaard N (1995) hCAP-18, a cathelin/pro-bactenecin-like protein of human neutrophil specific granules. FEBS Lett 368(1):173-176
47. Cowland JB, Sorensen OE, Sehested M, Borregaard N (2003) Neutrophil gelatinase-associated lipocalin is up-regulated in human epithelial cells by IL-1 beta, but not by TNF-alpha. J Immunol 171(12):6630-6639
48. Cruz CM, Rinna A, Forman HJ, Ventura AL, Persechini PM, Ojcius DM (2007) ATP activates a reactive oxygen species-dependent oxidative stress response and secretion of proinflammatory cytokines in macrophages. J Biol Chem 282(5):2871-2879
49. Daher KA, Selsted ME, Lehrer RI (1986) Direct inactivation of viruses by human granulocyte defensins. J Virol 60(3):1068-1074
50. Davis CW, Dickey BF (2008) Regulated airway goblet cell mucin secretion. Annu Rev Physiol 70:487-512
51. Decraene A, Willems-Widyastuti A, Kasran A, De Boeck K, Bullens DM, Dupont LJ (2010) Elevated expression of both mRNA and protein levels of IL-17A in sputum of stable Cystic Fibrosis patients. Respir Res 11:177
52. Derichs N, Jin BJ, Song Y, Finkbeiner WE, Verkman AS (2011) Hyperviscous airway periciliary and mucous liquid layers in cystic fibrosis measured by confocal fluorescence photobleaching. FASEB J 25(7):2325-2332
53. Di A, Brown ME, Deriy LV, Li C, Szeto FL, Chen Y, Huang P, Tong J, Naren AP, Bindokas V, Palfrey HC, Nelson DJ (2006) CFTR regulates phagosome acidification in macrophages and alters bactericidal activity. Nat Cell Biol 8(9):933-944
54. Do TQ, Moshkani S, Castillo P, Anunta S, Pogosyan A, Cheung A, Marbois B, Faull KF, Ernst W, Chiang SM, Fujii G, Clarke CF, Foster K, Porter E (2008) Lipids including cholesteryl linoleate and cholesteryl arachidonate contribute to the inherent antibacterial activity of human nasal fluid. J Immunol 181(6):4177-4187
55. Doring G, Albus A, Hoiby N (1988) Immunologic aspects of cystic fibrosis. Chest 94(2 Suppl):109S-115S
56. Dorschner RA, Lopez-Garcia B, Peschel A, Kraus D, Morikawa K, Nizet V, Gallo RL (2006) The mammalian ionic environment dictates microbial susceptibility to antimicrobial defense peptides. FASEB J 20(1):35-42
57. Dubin PJ, Kolls JK (2011) IL-17 in cystic fibrosis: more than just Th17 cells. Am J Respir Crit Care Med 184(2):155-157
58. Elsbach P, Weiss J, Franson RC, Beckerdite-Quagliata S, Schneider A, Harris L (1979) Separation and purification of a potent bactericidal/permeability-increasing protein and a closely associated phospholipase A2 from rabbit polymorphonuclear leukocytes. Observations on their relationship. J Biol Chem 254(21):11000-11009
59. Engelhardt JF, Yankaskas JR, Ernst SA, Yang Y, Marino CR, Boucher RC, Cohn JA, Wilson JM (1992) Submucosal glands are the predominant site of CFTR expression in the human bronchus. Nat Genet 2(3):240-248
60. Fanconi G, Uehlinger E, Knauer C (1936) Das Coeliakie-syndrom bei angeborener zystischer Pankreasfibromatose und Bronchiektasien (Celiac syndrome with congenital cystic fibromatosis of the pancreas and bronchiectasis). Wien Med Wchnschr 86:753-756
61. Felgentreff K, Beisswenger C, Griese M, Gulder T, Bringmann G, Bals R (2006) The antimicrobial peptide cathelicidin interacts with airway mucus. Peptides 27(12):3100-3106
62. Fiedler MA, Kaetzel CS, Davis PB (1991) Sustained production of secretory component by human tracheal epithelial cells in primary culture. Am J Physiol 261(4 Pt 1):L255-L261
63. Fischer H, Widdicombe JH (2006) Mechanisms of acid and base secretion by the airway epithelium. J Membr Biol 211(3):139-150
64. Fleming A (1922) On a remarkable bacteriolytic element found in tissues and secretions. Proc R Soc (Lond) 93:306-319
65. Fleming A, Allison VD (1922) Observations on a bacteriolytic substance ("lysozyme") found in secretions and tissues. Br J Exp Pathol 3:252-260
66. Fluckinger M, Haas H, Merschak P, Glasgow BJ, Redl B (2004) Human tear lipocalin exhibits antimicrobial activity by scavenging microbial siderophores. Antimicrob Agents Chemother 48(9):3367-3372
67. Forteza R, Salathe M, Miot F, Forteza R, Conner GE (2005) Regulated hydrogen peroxide production by Duox in human airway epithelial cells. Am J Respir Cell Mol Biol 32(5):462-469
68. Gakhar L, Bartlett JA, Penterman J, Mizrachi D, Singh PK, Mallampalli RK, Ramaswamy S, McCray PB Jr (2010) PLUNC is a novel airway surfactant protein with anti-biofilm activity. PLoS One 5(2):e9098
69. Ganz T, Selsted ME, Szklarek D, Harwig SS, Daher K, Bainton DF, Lehrer RI (1985) Defensins. Natural peptide antibiotics of human neutrophils. J Clin Invest 76(4):1427-1435
70. Garcia JR, Jaumann F, Schulz S, Krause A, Rodriguez-Jimenez J, Forssmann U, Adermann K, Kluver E, Vogelmeier C, Becker D, Hedrich R, Forssmann WG, Bals R (2001a) Identification of a novel, multifunctional beta-defensin (human beta-defensin 3) with specific antimicrobial activity. Its interaction with plasma membranes of Xenopus oocytes and the induction of macrophage chemoattraction. Cell Tissue Res 306(2):257-264
71. Garcia JR, Krause A, Schulz S, Rodriguez-Jimenez FJ, Kluver E, Adermann K, Forssmann U, Frimpong-Boateng A, Bals R, Forssmann WG (2001b) Human beta-defensin 4: a novel inducible peptide with a specific salt-sensitive spectrum of antimicrobial activity. FASEB J 15(10):1819-1821
72. Garred P, Pressler T, Madsen HO, Frederiksen B, Svejgaard A, Hoiby N, Schwartz M, Koch C (1999) Association of mannose-binding lectin gene heterogeneity with severity of lung disease and survival in cystic fibrosis. J Clin Invest 104(4):431-437
73. Gaskin KJ, Durie PR, Corey M, Wei P, Forstner GG (1982) Evidence for a primary defect of pancreatic HCO3-secretion in cystic fibrosis. Pediatr Res 16(7):554-557
74. Gerson C, Sabater J, Scuri M, Torbati A, Coffey R, Abraham JW, Lauredo I, Forteza R, Wanner A, Salathe M, Abraham WM, Conner GE (2000) The lactoperoxidase system functions in bacterial clearance of airways. Am J Respir Cell Mol Biol 22(6):665-671
75. Gilljam H, Ellin A, Strandvik B (1989) Increased bronchial chloride concentration in cystic fibrosis. Scand J Clin Lab Invest 49(2):121-124
76. Glaser R, Harder J, Lange H, Bartels J, Christophers E, Schroder JM (2005) Antimicrobial psoriasin (S100A7) protects human skin from Escherichia coli infection. Nat Immunol 6(1):57-64
77. Goetz DH, Holmes MA, Borregaard N, Bluhm ME, Raymond KN, Strong RK (2002) The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition. Mol Cell 10(5):1033-1043
78. Goldman MJ, Anderson GM, Stolzenberg ED, Kari UP, Zasloff M, Wilson JM (1997) Human beta-defensin-1 is a salt-sensitive antibiotic in lung that is inactivated in cystic fibrosis. Cell 88(4):553-560
79. Gottsch JD, Eisinger SW, Liu SH, Scott AL (1999) Calgranulin C has filariacidal and filariastatic activity. Infect Immun 67(12):6631-6636
80. Greene CM, McElvaney NG, O'Neill SJ, Taggart CC (2004) Secretory leucoprotease inhibitor impairs Toll-like receptor 2- and 4-mediated responses in monocytic cells. Infect Immun 72(6):3684-3687
81. Griesenbach U, Soussi S, Larsen MB, Casamayor I, Dewar A, Regamey N, Bush A, Shah PL, Davies JC, Alton EW (2011) Quantification of periciliary fluid height in human airway biopsies is feasible, but not suitable as a biomarker. Am J Respir Cell Mol Biol 44(3):309-315
82. Groneberg DA, Eynott PR, Oates T, Lim S, Wu R, Carlstedt I, Nicholson AG, Chung KF (2002) Expression of MUC5AC and MUC5B mucins in normal and cystic fibrosis lung. Respir Med 96(2):81-86
83. Grubb BR, Chadburn JL, Boucher RC (2002) In vivo microdialysis for determination of nasal liquid ion composition. Am J Physiol Cell Physiol 282(6):C1423-C1431
84. Guarda G, Braun M, Staehli F, Tardivel A, Mattmann C, Forster I, Farlik M, Decker T, Du Pasquier RA, Romero P, Tschopp J (2011) Type I interferon inhibits interleukin-1 production and inflammasome activation. Immunity 34(2):213-223
85. Guignard F, Mauel J, Markert M (1995) Identification and characterization of a novel human neutrophil protein related to the S100 family. Biochem J 309(Pt 2):395-401
86. Guyot N, Butler MW, McNally P, Weldon S, Greene CM, Levine RL, O'Neill SJ, Taggart CC, McElvaney NG (2008) Elafin, an elastase-specific inhibitor, is cleaved by its cognate enzyme neutrophil elastase in sputum from individuals with cystic fibrosis. J Biol Chem 283(47):32377-32385
87. Harder J, Bartels J, Christophers E, Schroder JM (2001) Isolation and characterization of human beta -defensin-3, a novel human inducible peptide antibiotic. J Biol Chem 276(8):5707-5713
88. Hartshorn KL, Crouch EC, White MR, Eggleton P, Tauber AI, Chang D, Sastry K (1994) Evidence for a protective role of pulmonary surfactant protein D (SP-D) against influenza A viruses. J Clin Invest 94(1):311-319
89. Hartshorn KL, Crouch E, White MR, Colamussi ML, Kakkanatt A, Tauber B, Shepherd V, Sastry KN (1998) Pulmonary surfactant proteins A and D enhance neutrophil uptake of bacteria. Am J Physiol 274(6 Pt 1):L958-L969
90. Heilborn JD, Nilsson MF, Kratz G, Weber G, Sorensen O, Borregaard N, Stahle-Backdahl M (2003) The cathelicidin anti-microbial peptide LL-37 is involved in re-epithelialization of human skin wounds and is lacking in chronic ulcer epithelium. J Invest Dermatol 120(3):379-389
91. Henriksen PA, Hitt M, Xing Z, Wang J, Haslett C, Riemersma RA, Webb DJ, Kotelevtsev YV, Sallenave JM (2004) Adenoviral gene delivery of elafin and secretory leukocyte protease inhibitor attenuates NF-kappa B-dependent inflammatory responses of human endothelial cells and macrophages to atherogenic stimuli. J Immunol 172(7):4535-4544
92. Henry MT, Cave S, Rendall J, O'Connor CM, Morgan K, FitzGerald MX, Kalsheker N (2001) An alpha1-antitrypsin enhancer polymorphism is a genetic modifier of pulmonary outcome in cystic fibrosis. Eur J Hum Genet 9(4):273-278
93. Hiatt RB, Engle C, Karush K (1952) The role of the granulocyte as a source of lysozyme in ulcerative colitis. J Clin Invest 31(7):721-726
94. Hiatt PW, Grace SC, Kozinetz CA, Raboudi SH, Treece DG, Taber LH, Piedra PA (1999) Effects of viral lower respiratory tract infection on lung function in infants with cystic fibrosis. Pediatrics 103(3):619-626
95. Hiemstra PS, Maassen RJ, Stolk J, Heinzel-Wieland R, Steffens GJ, Dijkman JH (1996) Antibacterial activity of antileukoprotease. Infect Immun 64(11):4520-4524
96. Holma B (1985) Influence of buffer capacity and pH-dependent rheological properties of respiratory mucus on health effects due to acidic pollution. Sci Total Environ 41(2):101-123
97. Hovenberg HW, Davies JR, Carlstedt I (1996) Different mucins are produced by the surface epithelium and the submucosa in human trachea: identification of MUC5AC as a major mucin from the goblet cells. Biochem J 318(Pt 1):319-324
98. Iovine NM, Elsbach P, Weiss J (1997) An opsonic function of the neutrophil bactericidal/ permeability-increasing protein depends on both its N- and C-terminal domains. Proc Natl Acad Sci USA 94(20):10973-10978
99. Isemura S, Saitoh E, Ito S, Isemura M, Sanada K (1984) Cystatin S: a cysteine proteinase inhibitor of human saliva. J Biochem 96(4):1311-1314
100. Itani OA, Chen JH, Karp PH, Ernst S, Keshavjee S, Parekh K, Klesney-Tait J, Zabner J, Welsh MJ (2011) Human cystic fibrosis airway epithelia have reduced Cl- conductance but not increased Na+ conductance. Proc Natl Acad Sci USA 108(25):10260-10265
101. Jayaraman S, Joo NS, Reitz B, Wine JJ, Verkman AS (2001a) Submucosal gland secretions in airways from cystic fibrosis patients have normal [Na(+)] and pH but elevated viscosity. Proc Natl Acad Sci USA 98(14):8119-8123
102. Jayaraman S, Song Y, Vetrivel L, Shankar L, Verkman AS (2001b) Noninvasive in vivo fluorescence measurement of airway-surface liquid depth, salt concentration, and pH. J Clin Invest 107(3):317-324
103. Jia HP, Schutte BC, Schudy A, Linzmeier R, Guthmiller JM, Johnson GK, Tack BF, Mitros JP, Rosenthal A, Ganz T, McCray PB Jr (2001) Discovery of new human beta-defensins using a genomics-based approach. Gene 263(1-2):211-218
104. Joo NS, Irokawa T, Wu JV, Robbins RC, Whyte RI, Wine JJ (2002) Absent secretion to vasoactive intestinal peptide in cystic fibrosis airway glands. J Biol Chem 277(52):50710-50715
105. Joo NS, Lee DJ, Winges KM, Rustagi A, Wine JJ (2004) Regulation of antiprotease and antimicrobial protein secretion by airway submucosal gland serous cells. J Biol Chem 279(37):38854-38860
106. Joo NS, Irokawa T, Robbins RC, Wine JJ (2006) Hyposecretion, not hyperabsorption, is the basic defect of cystic fibrosis airway glands. J Biol Chem 281(11):7392-7398
107. Joo NS, Cho HJ, Khansaheb M, Wine JJ (2010) Hyposecretion of fluid from tracheal submucosal glands of CFTR-deficient pigs. J Clin Invest 120(9):3161-3166
108. Joris L, Dab I, Quinton PM (1993) Elemental composition of human airway surface fluid in healthy and diseased airways. Am Rev Respir Dis 148(6 Pt 1):1633-1637
109. Kerem B, Rommens JM, Buchanan JA, Markiewicz D, Cox TK, Chakravarti A, Buchwald M, Tsui LC (1989) Identification of the cystic fibrosis gene: genetic analysis. Science 245(4922):1073-1080
110. Khan TZ, Wagener JS, Bost T, Martinez J, Accurso FJ, Riches DW (1995) Early pulmonary inflammation in infants with cystic fibrosis. Am J Respir Crit Care Med 151(4):1075-1082
111. King AE, Critchley HO, Sallenave JM, Kelly RW (2003) Elafin in human endometrium: an antiprotease and antimicrobial molecule expressed during menstruation. J Clin Endocrinol Metab 88(9):4426-4431
112. Kjeldsen L, Johnsen AH, Sengelov H, Borregaard N (1993) Isolation and primary structure of NGAL, a novel protein associated with human neutrophil gelatinase. J Biol Chem 268 (14):10425-10432
113. Klymiuk N, Mundhenk L, Kraehe K, Wuensch A, Plog S, Emrich D, Langenmayer MC, Stehr M, Holzinger A, Kroner C, Richter A, Kessler B, Kurome M, Eddicks M, Nagashima H, Heinritzi K, Gruber AD, Wolf E (2011) Sequential targeting of CFTR by BAC vectors generates a novel pig model of cystic fibrosis. J Mol Med (Berl) 90(5):597-608. doi:10.1007/s00109-011-0839-y
114. Knowles M, Gatzy J, Boucher R (1981) Increased bioelectric potential difference across respiratory epithelia in cystic fibrosis. N Engl J Med 305(25):1489-1495
115. Knowles M, Gatzy J, Boucher R (1983a) Relative ion permeability of normal and cystic fibrosis nasal epithelium. J Clin Invest 71(5):1410-1417
116. Knowles MR, Stutts MJ, Spock A, Fischer N, Gatzy JT, Boucher RC (1983b) Abnormal ion permeation through cystic fibrosis respiratory epithelium. Science 221(4615):1067-1070
117. Knowles MR, Robinson JM, Wood RE, Pue CA, Mentz WM, Wager GC, Gatzy JT, Boucher RC (1997) Ion composition of airway surface liquid of patients with cystic fibrosis as compared with normal and disease-control subjects. J Clin Invest 100(10):2588-2595
118. Koczulla R, von Degenfeld G, Kupatt C, Krotz F, Zahler S, Gloe T, Issbrucker K, Unterberger P, Zaiou M, Lebherz C, Karl A, Raake P, Pfosser A, Boekstegers P, Welsch U, Hiemstra PS, Vogelmeier C, Gallo RL, Clauss M, Bals R (2003) An angiogenic role for the human peptide antibiotic LL-37/hCAP-18. J Clin Invest 111(11):1665-1672
119. Kopelman H, Corey M, Gaskin K, Durie P, Weizman Z, Forstner G (1988) Impaired chloride secretion, as well as bicarbonate secretion, underlies the fluid secretory defect in the cystic fibrosis pancreas. Gastroenterology 95(2):349-355
120. Korfhagen TR, Bruno MD, Ross GF, Huelsman KM, Ikegami M, Jobe AH, Wert SE, Stripp BR, Morris RE, Glasser SW, Bachurski CJ, Iwamoto HS, Whitsett JA (1996) Altered surfactant function and structure in SP-A gene targeted mice. Proc Natl Acad Sci USA 93(18):9594-9599
121. Kozlova I, Nilsson H, Henriksnas J, Roomans GM (2006a) X-ray microanalysis of apical fluid in cystic fibrosis airway epithelial cell lines. Cell Physiol Biochem 17(1-2):13-20
122. Kozlova I, Vanthanouvong V, Johannesson M, Roomans GM (2006b) Composition of airway surface liquid determined by X-ray microanalysis. Ups J Med Sci 111(1):137-153
123. Kuan SF, Rust K, Crouch E (1992) Interactions of surfactant protein D with bacterial lipopolysaccharides. Surfactant protein D is an Escherichia coli-binding protein in bronchoalveolar lavage. J Clin Invest 90(1):97-106
124. Larrick JW, Hirata M, Balint RF, Lee J, Zhong J, Wright SC (1995) Human CAP18: a novel antimicrobial lipopolysaccharide-binding protein. Infect Immun 63(4):1291-1297
125. Lee KC, Eckert RL (2007) S100A7 (Psoriasin)-mechanism of antibacterial action in wounds. J Invest Dermatol 127(4):945-957
126. Lee RJ, Foskett JK (2010) cAMP-activated Ca2+ signaling is required for CFTR-mediated serous cell fluid secretion in porcine and human airways. J Clin Invest 120(9):3137-3148
127. Lehrer RI, Selsted ME, Szklarek D, Fleischmann J (1983) Antibacterial activity of microbicidal cationic proteins 1 and 2, natural peptide antibiotics of rabbit lung macrophages. Infect Immun 42(1):10-14
128. Lehrer RI, Ganz T, Szklarek D, Selsted ME (1988) Modulation of the in vitro candidacidal activity of human neutrophil defensins by target cell metabolism and divalent cations. J Clin Invest 81 (6):1829-1835
129. Leigh MW, Kylander JE, Yankaskas JR, Boucher RC (1995) Cell proliferation in bronchial epithelium and submucosal glands of cystic fibrosis patients. Am J Respir Cell Mol Biol 12(6):605-612
130. LeVine AM, Gwozdz J, Stark J, Bruno M, Whitsett J, Korfhagen T (1999a) Surfactant protein-A enhances respiratory syncytial virus clearance in vivo. J Clin Invest 103(7):1015-1021
131. LeVine AM, Kurak KE, Wright JR, Watford WT, Bruno MD, Ross GF, Whitsett JA, Korfhagen TR (1999b) Surfactant protein-A binds group B streptococcus enhancing phagocytosis and clearance from lungs of surfactant protein-A-deficient mice. Am J Respir Cell Mol Biol 20(2):279-286
132. LeVine AM, Whitsett JA, Gwozdz JA, Richardson TR, Fisher JH, Burhans MS, Korfhagen TR (2000) Distinct effects of surfactant protein A or D deficiency during bacterial infection on the lung. J Immunol 165(7):3934-3940
133. Li XL, Ezelle HJ, Kang TJ, Zhang L, Shirey KA, Harro J, Hasday JD, Mohapatra SK, Crasta OR, Vogel SN, Cross AS, Hassel BA (2008) An essential role for the antiviral endoribonuclease, RNase-L, in antibacterial immunity. Proc Natl Acad Sci USA 105(52):20816-20821
134. Lindahl M, Stahlbom B, Tagesson C (1999) Newly identified proteins in human nasal and bronchoalveolar lavage fluids: potential biomedical and clinical applications. Electrophoresis 20(18):3670-3676
135. Lindahl M, Stahlbom B, Tagesson C (2001) Identification of a new potential airway irritation marker, palate lung nasal epithelial clone protein, in human nasal lavage fluid with twodimensional electrophoresis and matrix-assisted laser desorption/ionization-time of flight. Electrophoresis 22(9):1795-1800
136. Lorentzen D, Durairaj L, Pezzulo AA, Nakano Y, Launspach J, Stoltz DA, Zamba G, McCray PB Jr, Zabner J, Welsh MJ, Nauseef WM, Banfi B (2011) Concentration of the antibacterial precursor thiocyanate in cystic fibrosis airway secretions. Free Radic Biol Med 50(9):1144-1150
137. Lukinskiene L, Liu Y, Reynolds SD, Steele C, Stripp BR, Leikauf GD, Kolls JK, Di YP (2011) Antimicrobial activity of PLUNC protects against Pseudomonas aeruginosa infection. J Immunol 187(1):382-390
138. Marra MN, Wilde CG, Griffith JE, Snable JL, Scott RW (1990) Bactericidal/permeability- increasing protein has endotoxin-neutralizing activity. J Immunol 144(2):662-666
139. Masson P, Heremans JF, Prignot J (1965) Immunohistochemical localization of the iron-binding protein lactoferrin in human bronchial glands. Experientia 21(10):604-605
140. Masson PL, Heremans JF, Prignot JJ, Wauters G (1966) Immunohistochemical localization and bacteriostatic properties of an iron-binding protein from bronchial mucus. Thorax 21(6):538-544
141. Masson PL, Heremans JF, Schonne E (1969) Lactoferrin, an iron-binding protein in neutrophilic leukocytes. J Exp Med 130(3):643-658
142. Matsui H, Grubb BR, Tarran R, Randell SH, Gatzy JT, Davis CW, Boucher RC (1998) Evidence for periciliary liquid layer depletion, not abnormal ion composition, in the pathogenesis of cystic fibrosis airways disease. Cell 95(7):1005-1015
143. McAllister F, Henry A, Kreindler JL, Dubin PJ, Ulrich L, Steele C, Finder JD, Pilewski JM, Carreno BM, Goldman SJ, Pirhonen J, Kolls JK (2005) Role of IL-17A, IL-17 F, and the IL-17 receptor in regulating growth-related oncogene-alpha and granulocyte colony-stimulating factor in bronchial epithelium: implications for airway inflammation in cystic fibrosis. J Immunol 175(1):404-412
144. McCray PB Jr, Bentley L (1997) Human airway epithelia express a beta-defensin. Am J Respir Cell Mol Biol 16(3):343-349
145. McGillivary G, Bakaletz LO (2010) The multifunctional host defense peptide SPLUNC1 is critical for homeostasis of the mammalian upper airway. PLoS One 5(10):e13224
146. Meyerholz DK, Stoltz DA, Namati E, Ramachandran S, Pezzulo AA, Smith AR, Rector MV, Suter MJ, Kao S, McLennan G, Tearney GJ, Zabner J, McCray PB Jr, Welsh MJ (2010) Loss of cystic fibrosis transmembrane conductance regulator function produces abnormalities in tracheal development in neonatal pigs and young children. Am J Respir Crit Care Med 182(10):1251-1261
147. Mihaila A, Tremblay GM (2001) Human alveolar macrophages express elafin and secretory leukocyte protease inhibitor. Z Naturforsch C 56(3-4):291-297
148. Moskwa P, Lorentzen D, Excoffon KJ, Zabner J, McCray PB Jr, Nauseef WM, Dupuy C, Banfi B (2007) A novel host defense system of airways is defective in cystic fibrosis. Am J Respir Crit Care Med 175(2):174-183
149. Mueller C, Braag SA, Keeler A, Hodges C, Drumm M, Flotte TR (2011) Lack of cystic fibrosis transmembrane conductance regulator in CD3+ lymphocytes leads to aberrant cytokine secretion and hyperinflammatory adaptive immune responses. Am J Respir Cell Mol Biol 44(6):922-929
150. Muhlebach MS, Stewart PW, Leigh MW, Noah TL (1999) Quantitation of inflammatory responses to bacteria in young cystic fibrosis and control patients. Am J Respir Crit Care Med 160 (1):186-191
151. Murakami S, Iwaki D, Mitsuzawa H, Sano H, Takahashi H, Voelker DR, Akino T, Kuroki Y (2002) Surfactant protein A inhibits peptidoglycan-induced tumor necrosis factor-alpha secretion in U937 cells and alveolar macrophages by direct interaction with toll-like receptor 2. J Biol Chem 277(9):6830-6837
152. Murthy AR, Lehrer RI, Harwig SS, Miyasaki KT (1993) In vitro candidastatic properties of the human neutrophil calprotectin complex. J Immunol 151(11):6291-6301
153. Nakagami Y, Favoreto S Jr, Zhen G, Park SW, Nguyenvu LT, Kuperman DA, Dolganov GM, Huang X, Boushey HA, Avila PC, Erle DJ (2008) The epithelial anion transporter pendrin is induced by allergy and rhinovirus infection, regulates airway surface liquid, and increases airway reactivity and inflammation in an asthma model. J Immunol 181(3):2203-2210
154. Nisapakultom K, Ross KF, Herzberg MC (2001a) Calprotectin expression in vitro by oral epithelial cells confers resistance to infection by Porphyromonas gingivalis. Infect Immun 69(7):4242-4247
155. Nisapakultorn K, Ross KF, Herzberg MC (2001b) Calprotectin expression inhibits bacterial binding to mucosal epithelial cells. Infect Immun 69(6):3692-3696
156. Niyonsaba F, Iwabuchi K, Someya A, Hirata M, Matsuda H, Ogawa H, Nagaoka I (2002) A cathelicidin family of human antibacterial peptide LL-37 induces mast cell chemotaxis. Immunology 106(1):20-26
157. Nordahl EA, Rydengard V, Nyberg P, Nitsche DP, Morgelin M, Malmsten M, Bjorck L, Schmidtchen A (2004) Activation of the complement system generates antibacterial peptides. Proc Natl Acad Sci USA 101(48):16879-16884
158. Oram JD, Reiter B (1968) Inhibition of bacteria by lactoferrin and other iron-chelating agents. Biochim Biophys Acta 170(2):351-365
159. Painter RG, Valentine VG, Lanson NA Jr, Leidal K, Zhang Q, Lombard G, Thompson C, Viswanathan A, Nauseef WM, Wang G, Wang G (2006) CFTR Expression in human neutrophils and the phagolysosomal chlorination defect in cystic fibrosis. Biochemistry (Mosc) 45(34):10260-10269
160. Painter RG, Bonvillain RW, Valentine VG, Lombard GA, LaPlace SG, Nauseef WM, Wang G (2008) The role of chloride anion and CFTR in killing of Pseudomonas aeruginosa by normal and CF neutrophils. J Leukoc Biol 83(6):1345-1353
161. Painter RG, Marrero L, Lombard GA, Valentine VG, Nauseef WM, Wang G (2010) CFTR- mediated halide transport in phagosomes of human neutrophils. J Leukoc Biol 87(5):933-942
162. Pazgier M, Hoover DM, Yang D, Lu W, Lubkowski J (2006) Human beta-defensins. Cell Mol Life Sci 63(11):1294-1313
163. Pedemonte N, Caci E, Sondo E, Caputo A, Rhoden K, Pfeffer U, Di Candia M, Bandettini R, Ravazzolo R, Zegarra-Moran O, Galietta LJ (2007) Thiocyanate transport in resting and IL-4- stimulated human bronchial epithelial cells: role of pendrin and anion channels. J Immunol 178(8):5144-5153
164. Pezzulo AA, Tang XX, Hoegger MJ, Abou Alaiwa MH, Ramachandran S, Moninger TO, Karp PH, Wohlford-Lenane CL, Haagsman HP, van Eijk M, Banfi B, Horswill AR, Stoltz DA, McCray PB Jr, Welsh MJ, Zabner J (2012) Reduced airway surface pH impairs bacterial killing in the porcine cystic fibrosis lung. Nature 487(7405):109-113
165. Phalipon A, Cardona A, Kraehenbuhl JP, Edelman L, Sansonetti PJ, Corthesy B (2002) Secretory component: a new role in secretory IgA-mediated immune exclusion in vivo. Immunity 17(1):107-115
166. Poeck H, Ruland J (2011) From virus to inflammation: mechanisms of RIG-I-induced IL-1beta production. Eur J Cell Biol 91(1):59-64
167. Poeck H, Bscheider M, Gross O, Finger K, Roth S, Rebsamen M, Hannesschlager N, Schlee M, Rothenfusser S, Barchet W, Kato H, Akira S, Inoue S, Endres S, Peschel C, Hartmann G, Hornung V, Ruland J (2010) Recognition of RNA virus by RIG-I results in activation of CARD9 and inflammasome signaling for interleukin 1 beta production. Nat Immunol 11(1):63-69
168. Pons G, Marchand MC, d'Athis P, Sauvage E, Foucard C, Chaumet-Riffaud P, Sautegeau A, Navarro J, Lenoir G (2000) French multicenter randomized double-blind placebo-controlled trial on nebulized amiloride in cystic fibrosis patients. The Amiloride-AFLM Collaborative Study Group. Pediatr Pulmonol 30(1):25-31
169. Porter EM, van Dam E, Valore EV, Ganz T (1997) Broad-spectrum antimicrobial activity of human intestinal defensin 5. Infect Immun 65(6):2396-2401
170. Poschet J, Perkett E, Deretic V (2002) Hyperacidification in cystic fibrosis: links with lung disease and new prospects for treatment. Trends Mol Med 8(11):512-519
171. Quinton PM (2008) Cystic fibrosis: impaired bicarbonate secretion and mucoviscidosis. Lancet 372(9636):415-417
172. Ramsey BW, Gore EJ, Smith AL, Cooney MK, Redding GJ, Foy H (1989) The effect of respiratory viral infections on patients with cystic fibrosis. Am J Dis Child 143(6):662-668
173. Redl B, Wojnar P, Ellemunter H, Feichtinger H (1998) Identification of a lipocalin in mucosal glands of the human tracheobronchial tree and its enhanced secretion in cystic fibrosis. Lab Invest 78(9):1121-1129
174. Robert R, Thoreau V, Norez C, Cantereau A, Kitzis A, Mettey Y, Rogier C, Becq F (2004) Regulation of the cystic fibrosis transmembrane conductance regulator channel by beta- adrenergic agonists and vasoactive intestinal peptide in rat smooth muscle cells and its role in vasorelaxation. J Biol Chem 279(20):21160-21168
175. Robert R, Norez C, Becq F (2005) Disruption of CFTR chloride channel alters mechanical properties and cAMP-dependent Cl- transport of mouse aortic smooth muscle cells. J Physiol 568(Pt 2):483-495
176. Rogan MP, Reznikov LR, Pezzulo AA, Gansemer ND, Samuel M, Prather RS, Zabner J, Fredericks DC, McCray PB Jr, Welsh MJ, Stoltz DA (2010) Pigs and humans with cystic fibrosis have reduced insulin-like growth factor 1 (IGF1) levels at birth. Proc Natl Acad Sci USA 107(47):20571-20575
177. Rogers CS, Hao Y, Rokhlina T, Samuel M, Stoltz DA, Li Y, Petroff E, Vermeer DW, Kabel AC, Yan Z, Spate L, Wax D, Murphy CN, Rieke A, Whitworth K, Linville ML, Korte SW, Engelhardt JF, Welsh MJ, Prather RS (2008a) Production of CFTR-null and CFTR-DeltaF508 heterozygous pigs by adeno-associated virus-mediated gene targeting and somatic cell nuclear transfer. J Clin Invest 118(4):1571-1577
178. Rogers CS, Stoltz DA, Meyerholz DK, Ostedgaard LS, Rokhlina T, Taft PJ, Rogan MP, Pezzulo AA, Karp PH, Itani OA, Kabel AC, Wohlford-Lenane CL, Davis GJ, Hanfland RA, Smith TL, Samuel M, Wax D, Murphy CN, Rieke A, Whitworth K, Uc A, Starner TD, Brogden KA, Shilyansky J, McCray PB Jr, Zabner J, Prather RS, Welsh MJ (2008b) Disruption of the CFTR gene produces a model of cystic fibrosis in newborn pigs. Science 321(5897):1837-1841
179. Rommens JM, Iannuzzi MC, Kerem B-S, Drumm ML, Melmer G, Dean M, Rozmahel R, Cole JL, Kennedy D, Hidaka N, Zsiga M, Buchwald M, Riordan JR, Tsui L-C, Collins FS (1989) Identification of the cystic fibrosis gene: chromosome walking and jumping. Science 245:1059-1065
180. Rosenfeld M, Gibson RL, McNamara S, Emerson J, Burns JL, Castile R, Hiatt P, McCoy K, Wilson CB, Inglis A, Smith A, Martin TR, Ramsey BW (2001) Early pulmonary infection, inflammation, and clinical outcomes in infants with cystic fibrosis. Pediatr Pulmonol 32(5):356-366
181. Rosenthal MD, Gordon MN, Buescher ES, Slusser JH, Harris LK, Franson RC (1995) Human neutrophils store type II 14-kDa phospholipase A2 in granules and secrete active enzyme in response to soluble stimuli. Biochem Biophys Res Commun 208(2):650-656
182. Rowe SM, Miller S, Sorscher EJ (2005) Cystic fibrosis. N Engl J Med 352(19):1992-2001
183. Ryckman C, Vandal K, Rouleau P, Talbot M, Tessier PA (2003) Proinflammatory activities of S100: proteins S100A8, S100A9, and S100A8/A9 induce neutrophil chemotaxis and adhesion. J Immunol 170(6):3233-3242
184. Saitoh H, Masuda T, Shimura S, Fushimi T, Shirato K (2001) Secretion and gene expression of secretory leukocyte protease inhibitor by human airway submucosal glands. Am J Physiol Lung Cell Mol Physiol 280(1):L79-L87
185. Salinas D, Haggie PM, Thiagarajah JR, Song Y, Rosbe K, Finkbeiner WE, Nielson DW, Verkman AS (2005) Submucosal gland dysfunction as a primary defect in cystic fibrosis. FASEB J 19(3):431-433
186. Sallenave JM (2010) Secretory leukocyte protease inhibitor and elafin/trappin-2: versatile mucosal antimicrobials and regulators of immunity. Am J Respir Cell Mol Biol 42(6):635-643
187. Sallenave JM, Shulmann J, Crossley J, Jordana M, Gauldie J (1994) Regulation of secretory leukocyte proteinase inhibitor (SLPI) and elastase-specific inhibitor (ESI/elafin) in human airway epithelial cells by cytokines and neutrophilic enzymes. Am J Respir Cell Mol Biol 11(6):733-741
188. Sallenave JM, Si Tahar M, Cox G, Chignard M, Gauldie J (1997) Secretory leukocyte proteinase inhibitor is a major leukocyte elastase inhibitor in human neutrophils. J Leukoc Biol 61(6):695-702
189. Salvatore F, Scudiero O, Castaldo G (2002) Genotype-phenotype correlation in cystic fibrosis: the role of modifier genes. Am J Med Genet 111(1):88-95
190. Sano H, Sohma H, Muta T, Nomura S, Voelker DR, Kuroki Y (1999) Pulmonary surfactant protein A modulates the cellular response to smooth and rough lipopolysaccharides by interaction with CD14. J Immunol 163(1):387-395
191. Sano H, Nagai K, Tsutsumi H, Kuroki Y (2003) Lactoferrin and surfactant protein A exhibit distinct binding specificity to F protein and differently modulate respiratory syncytial virus infection. Eur J Immunol 33(10):2894-2902
192. Sato M, Sano H, Iwaki D, Kudo K, Konishi M, Takahashi H, Takahashi T, Imaizumi H, Asai Y, Kuroki Y (2003) Direct binding of Toll-like receptor 2 to zymosan, and zymosan-induced NF-kappa B activation and TNF-alpha secretion are down-regulated by lung collectin surfactant protein A. J Immunol 171(1):417-425
193. Schutte BC, McCray PB Jr (2002) [beta]-defensins in lung host defense. Annu Rev Physiol 64:709-748
194. Selsted ME, Szklarek D, Ganz T, Lehrer RI (1985) Activity of rabbit leukocyte peptides against Candida albicans. Infect Immun 49(1):202-206
195. Sibley CD, Surette MG (2011) The polymicrobial nature of airway infections in cystic fibrosis: Cangene Gold Medal Lecture. Can J Microbiol 57(2):69-77
196. Simpson AJ, Maxwell AI, Govan JR, Haslett C, Sallenave JM (1999) Elafin (elastase-specific inhibitor) has anti-microbial activity against gram-positive and gram-negative respiratory pathogens. FEBS Lett 452(3):309-313
197. Singh PK, Jia HP, Wiles K, Hesselberth J, Liu L, Conway BA, Greenberg EP, Valore EV, Welsh MJ, Ganz T, Tack BF, McCray PB Jr (1998) Production of beta-defensins by human airway epithelia. Proc Natl Acad Sci USA 95(25):14961-14966
198. Singh PK, Schaefer AL, Parsek MR, Moninger TO, Welsh MJ, Greenberg EP (2000a) Quorumsensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms. Nature 407(6805):762-764
199. Singh PK, Tack BF, McCray PB Jr, Welsh MJ (2000b) Synergistic and additive killing by antimicrobial factors found in human airway surface liquid. Am J Physiol Lung Cell Mol Physiol 279(5):L799-L805
200. Smith JJ, Welsh MJ (1992) cAMP stimulates bicarbonate secretion across normal, but not cystic fibrosis airway epithelia. J Clin Invest 89(4):1148-1153
201. Smith JJ, Travis SM, Greenberg EP, Welsh MJ (1996) Cystic fibrosis airway epithelia fail to kill bacteria because of abnormal airway surface fluid. Cell 85(2):229-236
202. Sohnle PG, Collins-Lech C, Wiessner JH (1991) The zinc-reversible antimicrobial activity of neutrophil lysates and abscess fluid supernatants. J Infect Dis 164(1):137-142
203. Sohnle PG, Hahn BL, Santhanagopalan V (1996) Inhibition of Candida albicans growth by calprotectin in the absence of direct contact with the organisms. J Infect Dis 174(6):1369-1372
204. Sonesson A, Ringstad L, Nordahl EA, Malmsten M, Morgelin M, Schmidtchen A (2007) Antifungal activity of C3a and C3a-derived peptides against Candida. Biochim Biophys Acta 1768 (2):346-353
205. Song Y, Salinas D, Nielson DW, Verkman AS (2006) Hyperacidity of secreted fluid from submucosal glands in early cystic fibrosis. Am J Physiol Cell Physiol 290(3):C741-C749
206. Sorensen O, Arnljots K, Cowland JB, Bainton DF, Borregaard N (1997) The human antibacterial cathelicidin, hCAP-18, is synthesized in myelocytes and metamyelocytes and localized to specific granules in neutrophils. Blood 90(7):2796-2803
207. Starner TD, Barker CK, Jia HP, Kang Y, McCray PB Jr (2003) CCL20 is an inducible product of human airway epithelia with innate immune properties. Am J Respir Cell Mol Biol 29(5):627-633
208. Steinbakk M, Naess-Andresen CF, Lingaas E, Dale I, Brandtzaeg P, Fagerhol MK (1990) Antimicrobial actions of calcium binding leucocyte L1 protein, calprotectin. Lancet 336(8718):763-765
209. Stoltz DA, Meyerholz DK, Pezzulo AA, Ramachandran S, Rogan MP, Davis GJ, Hanfland RA, Wohlford-Lenane C, Dohrn CL, Bartlett JA, Nelson GA, Chang EH, Taft PJ, Ludwig PS, Estin M, Hornick EE, Launspach JL, Samuel M, Rokhlina T, Karp PH, Ostedgaard LS, Uc A, Starner TD, Horswill AR, Brogden KA, Prather RS, Richter SS, Shilyansky J, McCray PB Jr, Zabner J, Welsh MJ (2010) Cystic fibrosis pigs develop lung disease and exhibit defective bacterial eradication at birth. Sci Transl Med 2(29):29-31
210. Strunk T, Richmond P, Prosser A, Simmer K, Levy O, Burgner D, Currie A (2011) Method of bacterial killing differentially affects the human innate immune response to Staphylococcus epidermidis. Innate Immun 17(6):508-516
211. Sun X, Yan Z, Yi Y, Li Z, Lei D, Rogers CS, Chen J, Zhang Y, Welsh MJ, Leno GH, Engelhardt JF (2008) Adeno-associated virus-targeted disruption of the CFTR gene in cloned ferrets. J Clin Invest 118(4):1578-1583
212. Sun X, Sui H, Fisher JT, Yan Z, Liu X, Cho HJ, Joo NS, Zhang Y, Zhou W, Yi Y, Kinyon JM, Lei-Butters DC, Griffin MA, Naumann P, Luo M, Ascher J, Wang K, Frana T, Wine JJ, Meyerholz DK, Engelhardt JF (2010) Disease phenotype of a ferret CFTR-knockout model of cystic fibrosis. J Clin Invest 120(9):3149-3160
213. Sutanto EN, Kicic A, Foo CJ, Stevens PT, Mullane D, Knight DA, Stick SM (2011) Innate inflammatory responses of pediatric cystic fibrosis airway epithelial cells: effects of nonviral and viral stimulation. Am J Respir Cell Mol Biol 44(6):761-767
214. Tabcharani JA, Rommens JM, Hou YX, Chang XB, Tsui LC, Riordan JR, Hanrahan JW (1993) Multi-ion pore behaviour in the CFTR chloride channel. Nature 366(6450):79-82
215. Taggart CC, Greene CM, Smith SG, Levine RL, McCray PB Jr, O'Neill S, McElvaney NG (2003) Inactivation of human beta-defensins 2 and 3 by elastolytic cathepsins. J Immunol 171(2):931-937
216. Tan HL, Regamey N, Brown S, Bush A, Lloyd CM, Davies JC (2011) The th17 pathway in cystic fibrosis lung disease. Am J Respir Crit Care Med 184(2):252-258
217. Tenner AJ, Robinson SL, Borchelt J, Wright JR (1989) Human pulmonary surfactant protein (SP-A), a protein structurally homologous to C1q, can enhance FcR- and CR1-mediated phagocytosis. J Biol Chem 264(23):13923-13928
218. Territo MC, Ganz T, Selsted ME, Lehrer R (1989) Monocyte-chemotactic activity of defensins from human neutrophils. J Clin Invest 84(6):2017-2020
219. Tjabringa GS, Ninaber DK, Drijfhout JW, Rabe KF, Hiemstra PS (2006) Human cathelicidin LL-37 is a chemoattractant for eosinophils and neutrophils that acts via formyl-peptide receptors. Int Arch Allergy Immunol 140(2):103-112
220. Travis SM, Conway BA, Zabner J, Smith JJ, Anderson NN, Singh PK, Greenberg EP, Welsh MJ (1999) Activity of abundant antimicrobials of the human airway. Am J Respir Cell Mol Biol 20(5):872-879
221. Triebel S, Blaser J, Reinke H, Tschesche H (1992) A 25 kDa alpha 2-microglobulin-related protein is a component of the 125 kDa form of human gelatinase. FEBS Lett 314(3):386-388
222. Turner J, Cho Y, Dinh NN, Waring AJ, Lehrer RI (1998) Activities of LL-37, a cathelin-associated antimicrobial peptide of human neutrophils. Antimicrob Agents Chemother 42(9):2206-2214
223. Valore EV, Park CH, Quayle AJ, Wiles KR, McCray PB Jr, Ganz T (1998) Human beta-defensin- 1: an antimicrobial peptide of urogenital tissues. J Clin Invest 101(8):1633-1642
224. van Iwaarden F, Welmers B, Verhoef J, Haagsman HP, van Golde LM (1990) Pulmonary surfactant protein A enhances the host-defense mechanism of rat alveolar macrophages. Am J Respir Cell Mol Biol 2(1):91-98
225. van Iwaarden JF, van Strijp JA, Ebskamp MJ, Welmers AC, Verhoef J, van Golde LM (1991) Surfactant protein A is opsonin in phagocytosis of herpes simplex virus type 1 by rat alveolar macrophages. Am J Physiol 261(2 Pt 1):L204-L209
226. Van Iwaarden JF, Pikaar JC, Storm J, Brouwer E, Verhoef J, Oosting RS, van Golde LM, van Strijp JA (1994) Binding of surfactant protein A to the lipid A moiety of bacterial lipopolysaccharides. Biochem J 303(Pt 2):407-411
227. van't Hof W, Blankenvoorde MF, Veerman EC, Amerongen AV (1997) The salivary lipocalin von Ebner's gland protein is a cysteine proteinase inhibitor. J Biol Chem 272(3):1837-1841
228. Vandal K, Rouleau P, Boivin A, Ryckman C, Talbot M, Tessier PA (2003) Blockade of S100A8 and S100A9 suppresses neutrophil migration in response to lipopolysaccharide. J Immunol 171(5):2602-2609
229. Vandebrouck C, Melin P, Norez C, Robert R, Guibert C, Mettey Y, Becq F (2006) Evidence that CFTR is expressed in rat tracheal smooth muscle cells and contributes to bronchodilation. Respir Res 7:113
230. Vanthanouvong V, Kozlova I, Johannesson M, Naas E, Nordvall SL, Dragomir A, Roomans GM (2006) Composition of nasal airway surface liquid in cystic fibrosis and other airway diseases determined by X-ray microanalysis. Microsc Res Tech 69(4):271-276
231. Weinrauch Y, Elsbach P, Madsen LM, Foreman A, Weiss J (1996) The potent anti-Staphylococcus aureus activity of a sterile rabbit inflammatory fluid is due to a 14-kD phospholipase A2. J Clin Invest 97(1):250-257
232. Weiss J, Elsbach P, Olsson I, Odeberg H (1978) Purification and characterization of a potent bactericidal and membrane active protein from the granules of human polymorphonuclear leukocytes. J Biol Chem 253(8):2664-2672
233. Weldon S, McNally P, McElvaney NG, Elborn JS, McAuley DF, Wartelle J, Belaaouaj A, Levine RL, Taggart CC (2009) Decreased levels of secretory leucoprotease inhibitor in the Pseudomonas-infected cystic fibrosis lung are due to neutrophil elastase degradation. J Immunol 183(12):8148-8156
234. Welsh MJ, Ramsey BW, Accurso F, Cutting GR (2001) Cystic fibrosis. In: Scriver CR, Beaudet AL, Sly WS, Valle D, Childs B, Vogelstein B (eds) The metabolic and molecular basis of inherited disease, vol 3, 8th edn. McGraw-Hill, New York, NY, pp 5121-5189
235. Wijkstrom-Frei C, El-Chemaly S, Ali-Rachedi R, Gerson C, Cobas MA, Forteza R, Salathe M, Conner GE (2003) Lactoperoxidase and human airway host defense. Am J Respir Cell Mol Biol 29(2):206-212
236. Wilkinson TS, Dhaliwal K, Hamilton TW, Lipka AF, Farrell L, Davidson DJ, Duffin R, Morris AC, Haslett C, Govan JR, Gregory CD, Sallenave JM, Simpson AJ (2009) Trappin-2 promotes early clearance of Pseudomonas aeruginosa through CD14-dependent macrophage activation and neutrophil recruitment. Am J Pathol 174(4):1338-1346
237. Wine JJ, Joo NS (2004) Submucosal glands and airway defense. Proc Am Thorac Soc 1(1):47-53
238. Wright FA, Strug LJ, Doshi VK, Commander CW, Blackman SM, Sun L, Berthiaume Y, Cutler D, Cojocaru A, Collaco JM, Corey M, Dorfman R, Goddard K, Green D, Kent JW Jr, Lange EM, Lee S, Li W, Luo J, Mayhew GM, Naughton KM, Pace RG, Pare P, Rommens JM, Sandford A, Stonebraker JR, Sun W, Taylor C, Vanscoy LL, Zou F, Blangero J, Zielenski J, O'Neal WK, Drumm ML, Durie PR, Knowles MR, Cutting GR (2011) Genome-wide association and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2. Nat Genet 43(6):539-546
239. Xu YY, Samaranayake YH, Samaranayake LP, Nikawa H (1999) In vitro susceptibility of Candida species to lactoferrin. Med Mycol 37(1):35-41
240. Yang D, Chertov O, Bykovskaia SN, Chen Q, Buffo MJ, Shogan J, Anderson M, Schroder JM, Wang JM, Howard OM, Oppenheim JJ (1999) Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science 286(5439):525-528
241. Yang D, Chen Q, Schmidt AP, Anderson GM, Wang JM, Wooters J, Oppenheim JJ, Chertov O (2000) LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells. J Exp Med 192(7):1069-1074
242. Yang D, Chen Q, Hoover DM, Staley P, Tucker KD, Lubkowski J, Oppenheim JJ (2003) Many chemokines including CCL20/MIP-3alpha display antimicrobial activity. J Leukoc Biol 74(3):448-455
243. Yoneyama M, Kikuchi M, Natsukawa T, Shinobu N, Imaizumi T, Miyagishi M, Taira K, Akira S, Fujita T (2004) The RNA helicase RIG-I has an essential function in double-stranded RNA- induced innate antiviral responses. Nat Immunol 5(7):730-737
244. Yoshida M, Korfhagen TR, Whitsett JA (2001) Surfactant protein D regulates NF-kappa B and matrix metalloproteinase production in alveolar macrophages via oxidant-sensitive pathways. J Immunol 166(12):7514-7519
245. Zabner J, Smith JJ, Karp PH, Widdicombe JH, Welsh MJ (1998) Loss of CFTR chloride channels alters salt absorption by cystic fibrosis airway epithelia in vitro. Mol Cell 2(3):397-403
246. Zallen G, Moore EE, Johnson JL, Tamura DY, Barkin M, Stockinger H, Silliman CC (1998) New mechanisms by which secretory phospholipase A2 stimulates neutrophils to provoke the release of cytotoxic agents. Arch Surg 133(11):1229-1233
247. Zhang Y, Li X, Grassme H, Doring G, Gulbins E (2010) Alterations in ceramide concentration and pH determine the release of reactive oxygen species by Cftr-deficient macrophages on infection. J Immunol 184(9):5104-5111
248. Zheng S, De BP, Choudhary S, Comhair SA, Goggans T, Slee R, Williams BR, Pilewski J, Haque SJ, Erzurum SC (2003) Impaired innate host defense causes susceptibility to respiratory virus infections in cystic fibrosis. Immunity 18(5):619-630
249. Zhou HD, Li XL, Li GY, Zhou M, Liu HY, Yang YX, Deng T, Ma J, Sheng SR (2008) Effect of SPLUNC1 protein on the Pseudomonas aeruginosa and Epstein-Barr virus. Mol Cell Biochem 309(1-2):191-197