Cystic fibrosis airway secretions exhibit mucin hyperconcentration and increased osmotic pressure

Journal of Clinical Investigation

Volumn 124, Issue 7, 2014, Pages 3047-3060

  Henderson, Ashley G ^a   Ehre, Camille ^a   Button, Brian ^a   Abdullah, Lubna H ^a   Cai, Li Heng ^b   Leigh, Margaret W ^a   DeMaria, Genevieve C ^a   Matsui, Hiro ^a   Donaldson, Scott H ^a   Davis, C William ^a   Sheehan, John K ^a   Boucher, Richard C ^a   Kesimer, Mehmet ^a  

^a UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^b University of North Carolina at Chapel Hill   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

LACTOFERRIN; LEUKOCYTE ELASTASE; MESSENGER RNA; MUCIN; MUCIN 5AC; MUCIN 5B;

AGAR GEL ELECTROPHORESIS; ARTICLE; BRONCHIOLE; BRONCHUS; CONTROLLED STUDY; CYSTIC FIBROSIS; GEL PERMEATION CHROMATOGRAPHY; GENE EXPRESSION; HUMAN; HUMAN TISSUE; IMMUNODETECTION; MUCUS SECRETION; OSMOTIC PRESSURE; PRIORITY JOURNAL; PROTEIN DEGRADATION; REAL TIME POLYMERASE CHAIN REACTION; SPUTUM;

ADULT; CASE-CONTROL STUDIES; CHILD; CHROMATOGRAPHY, GEL; CYSTIC FIBROSIS; FEMALE; HUMANS; IMMUNOASSAY; LEUKOCYTE ELASTASE; MALE; MASS SPECTROMETRY; MIDDLE AGED; MOLECULAR WEIGHT; MUCIN-5B; MUCINS; OSMOTIC PRESSURE; PROTEOLYSIS; PSEUDOMONAS AERUGINOSA; PSEUDOMONAS INFECTIONS; REPRODUCIBILITY OF RESULTS; RESPIRATORY SYSTEM; SPUTUM; YOUNG ADULT;

EID: 84903759350     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI73469     Document Type: Article

References (49)

1. Davis PB. Cystic fibrosis since 1938. Am J Respir Crit Care Med. 2006;173(5):475-482.
2. Button B, et al. A periciliary brush promotes the lung health by separating the mucus layer from airway epithelia. Science. 2012;337(6097):937- 941.
3. Fahy JV, Dickey BF. Airway mucus function and dysfunction. N Engl J Med. 2010;363(23):2233-2247.
4. Stoltz DA, et al. Cystic fibrosis pigs develop lung disease and exhibit defective bacterial eradication at birth. Sci Transl Med. 2010;2(29):29ra31.
5. Mott LS, et al. Distribution of early structural lung changes due to cystic fibrosis detected with chest computed tomography. J Pediatr. 2013; 163(1):243-248 e243.
6. Smith JJ, Travis SM, Greenberg EP, Welsh MJ. Cystic fibrosis airway epithelia fail to kill bacteria because of abnormal airway surface fluid. Cell. 1996;85(2):229-236.
7. Pezzulo AA, et al. Reduced airway surface pH impairs bacterial killing in the porcine cystic fibrosis lung. Nature. 2012;487(7405):109-113.
8. Ganz T. Antimicrobial polypeptides in host defense of the respiratory tract. J Clin Invest. 2002; 109(6):693-697.
9. Puchelle E, Bajolet O, Abely M. Airway mucus in cystic fibrosis. Paediatr Respir Rev. 2002;3(2):115-119.
10. Rose MC, Brown CF, Jacoby JZ, Jacoby JZ 3rd, Lynn WS, Kaufman B. Biochemical properties of tracheobronchial mucins from cystic fibrosis and non-cystic fibrosis individuals. Pediatr Res. 1987; 22(5):545-551.
11. Litt M, Khan MA, Chakrin LW, Wardell JR, Wardell JR Jr, Christian P. The viscoelasticity of fractionated canine tracheal mucus. Biorheology. 1974; 11(2):111-117.
12. Hovenberg HW, Davies JR, Carlstedt I. 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. 1996;318(pt 1):319-324.
13. Davies JR, Svitacheva N, Lannefors L, Kornfalt R, Carlstedt I. Identification of MUC5B, MUC5AC and small amounts of MUC2 mucins in cystic fibrosis airway secretions. Biochem J. 1999;344(pt 2):321-330.
14. Matsui H, et al. Evidence for periciliary liquid layer depletion, not abnormal ion composition, in the pathogenesis of cystic fibrosis airways disease. Cell. 1998;95(7):1005-1015.
15. Burgel PR, Montani D, Danel C, Dusser DJ, Nadel JA. A morphometric study of mucins and small airway plugging in cystic fibrosis. Thorax. 2007;62(2):153-161.
16. Henke MO, John G, Germann M, Lindemann H, Rubin BK. MUC5AC and MUC5B mucins increase in cystic fibrosis airway secretions during pulmonary exacerbation. Am J Respir Crit Care Med. 2007;175(8):816-821.
17. Henke MO, Renner A, Huber RM, Seeds MC, Rubin BK. MUC5AC and MUC5B mucins are decreased in cystic fibrosis airway secretions. Am J Respir Cell Mol Biol. 2004;31(1):86-91.
18. Henke MO, John G, Rheineck C, Chillappagari S, Naehrlich L, Rubin BK. Serine proteases degrade airway mucins in cystic fibrosis. Infect Immun. 2011;79(8):3438-3444.
19. Boat TF, Cheng PW, Iyer RN, Carlson DM, Polony I. Human respiratory tract secretion. Mucous glycoproteins of nonpurulent tracheobronchial secretions, and sputum of patients with bronchitis and cystic fibrosis. Arch Biochem Biophys. 1976;177(1):95-104.
20. Houdret N, et al. Evidence for the in vivo degradation of human respiratory mucins during Pseudomonas aeruginosa infection. Biochimica Biophys Acta. 1989;992(1):96-105.
21. Sagel SD, Chmiel JF, Konstan MW. Sputum biomarkers of inflammation in cystic fibrosis lung disease. Proc Am Thorac Soc. 2007;4(4):406-417.
22. Sagel SD, Wagner BD, Anthony MM, Emmett P, Zemanick ET. Sputum biomarkers of inflammation and lung function decline in children with cystic fibrosis. Am J Respir Crit Care Med. 2012; 186(9):857-865.
23. Thornton DJ, et al. Salivary mucin MG1 is comprised almost entirely of different glycosylated forms of the MUC5B gene product. Glycobiology. 1999;9(3):293-302.
24. Kesimer M, Sheehan JK. Analyzing the functions of large glycoconjugates through the dissipative properties of their absorbed layers using the gelforming mucin MUC5B as an example. Glycobiology. 2008;18(6):463-472.
25. Houdret N, et al. Evidence for the in vivo degradation of human respiratory mucins during Pseudomonas aeruginosa infection. Biochim Biophys Acta. 1989;992(1):96-105.
26. Matsui H, et al. A physical linkage between cystic fibrosis airway surface dehydration and Pseudomonas aeruginosa biofilms. Proc Natl Acad Sci U S A. 2006;103(48):18131-18136.
27. Pearson JP, Pesci EC, Iglewski BH. Roles of Pseudomonas aeruginosa las and rhl quorum-sensing systems in control of elastase and rhamnolipid biosynthesis genes. J Bacteriol. 1997;179(18):5756-5767.
28. Thornton DJ, et al. Identification of a nonmucin glycoprotein (gp-340) from a purified respiratory mucin preparation: evidence for an association involving the MUC5B mucin. Glycobiology. 2001;11(11):969-977.
29. Voynow JA, Gendler SJ, Rose MC. Regulation of mucin genes in chronic inflammatory airway diseases. Am J Respir Cell Mol Biol. 2006;34(6):661-665.
30. Ribeiro CM, et al. Chronic airway infection/inflammation induces a Ca2+i-dependent hyperinflammatory response in human cystic fibrosis airway epithelia. J Biol Chem. 2005;280(18):17798-17806.
31. Livraghi-Butrico A, et al. Mucus clearance, MyD88-dependent and MyD88-independent immunity modulate lung susceptibility to spontaneous bacterial infection and inflammation. Mucosal Immunol. 2012;5(4):397-408.
32. Hogg JC, et al. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med. 2004;350(26):2645-2653.
33. Cao R, Wang TT, DeMaria G, Sheehan JK, Kesimer M. Mapping the protein domain structures of the respiratory mucins: a mucin proteome coverage study. J Proteome Res. 2012;11(8):4013-4023.
34. Sly PD, et al. Risk factors for bronchiectasis in children with cystic fibrosis. N Engl J Med. 2013; 368(21):1963-1970.
35. Kesimer M, et al. Tracheobronchial air-liquid interface cell culture: a model for innate mucosal defense of the upper airways? Am J Physiol Lung Cell Mol Physiol. 2009;296(1):L92-L100.
36. Kesimer M, Ehre C, Burns KA, Davis CW, Sheehan JK, Pickles RJ. Molecular organization of the mucins and glycocalyx underlying mucus transport over mucosal surfaces of the airways. Mucosal Immunol. 2013;6(2):379-392.
37. Boucher RC. Airway surface dehydration in cystic fibrosis: pathogenesis and therapy. Annu Rev Med. 2007;58:157-170.
38. Hays SR, Fahy JV. Characterizing mucous cell remodeling in cystic fibrosis: relationship to neutrophils. Am J Respir Crit Care Med. 2006; 174(9):1018-1024.
39. Feather EA, Russell G. Sputum viscosity in cystic fibrosis of the pancreas and other pulmonary diseases. Br J Dis Chest. 1970;64(4):192-200.
40. Muhlebach MS, Stewart PW, Leigh MW, Noah TL. Quantitation of inflammatory responses to bacteria in young cystic fibrosis and control patients. Am J Respir Crit Care Med. 1999;160(1):186-191.
41. Fulcher ML, Gabriel S, Burns KA, Yankaskas JR, Randell SH. Well-differentiated human airway epithelial cell cultures. Methods Mol Med. 2005; 107:183-206.
42. Holmen JM, et al. Mucins and their O-Glycans from human bronchial epithelial cell cultures. Am J Physiol Lung Cell Mol Physiol. 2004;287(4):L824-L834.
43. Thornton DJ, Gray T, Nettesheim P, Howard M, Koo JS, Sheehan JK. Characterization of mucins from cultured normal human tracheobronchial epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2000;278(6):L1118-L1128.
44. Rousseau K, Wickstrom C, Whitehouse DB, Carlstedt I, Swallow DM. New monoclonal antibodies to non-glycosylated domains of the secreted mucins MUC5B and MUC7. Hybrid Hybridomics. 2003;22(5):293-299.
45. Kesimer M, Sheehan JK. Mass spectrometric analysis of mucin core proteins. Methods Mol Biol. 2012;842:67-79.
46. Thornton DJ, Carlstedt I, Sheehan JK. Identification of glycoproteins on nitrocellulose membranes and gels. Methods Mol Biol. 1994;32:119-128.
47. Jumel K, Fiebrig I, Harding SE. Rapid size distribution and purity analysis of gastric mucus glycoproteins by size exclusion chromatography/multi angle laser light scattering. Int J Biol Macromol. 1996;18(1-2):133-139.
48. Lidell ME, Bara J, Hansson GC. Mapping of the 45M1 epitope to the C-terminal cysteine-rich part of the human MUC5AC mucin. FEBS J. 2008;275(3):481-489.
49. Zhu Y, et al. Munc13-2-/-baseline secretion defect reveals source of oligomeric mucins in mouse airways. J Physiol. 2008;586(7):1977-1992.