With friends like these: The complex role of neutrophils in the progression of severe pneumonia

Frontiers in Cellular and Infection Microbiology

Volumn 7, Issue MAY, 2017, Pages

  Pechous, Roger D ^a  

^a UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES   (United States)

Author keywords

Neutrophils; Pneumonia; Pulmonary damage; Pulmonary immunity; Pulmonary infection

Indexed keywords

ANTIMICROBIAL CATIONIC PEPTIDE; CYTOKINE; REACTIVE OXYGEN METABOLITE; SERINE PROTEINASE;

CELL MOTION; DISEASE EXACERBATION; HUMAN; IMMUNOLOGY; INFLAMMATION; INNATE IMMUNITY; LEUKOCYTE ACTIVATION; LUNG; LUNG INFARCTION; LUNG INJURY; METABOLISM; MICROBIOLOGY; NEUTROPHIL; PHAGOCYTOSIS; PHYSIOLOGY; PNEUMONIA;

ANTIMICROBIAL CATIONIC PEPTIDES; CELL MOVEMENT; CYTOKINES; DISEASE PROGRESSION; HUMANS; IMMUNITY, INNATE; INFLAMMATION; LUNG; LUNG INJURY; NEUTROPHIL ACTIVATION; NEUTROPHILS; PHAGOCYTOSIS; PNEUMONIA; PULMONARY INFARCTION; REACTIVE OXYGEN SPECIES; SERINE PROTEASES;

EID: 85026892638     PISSN: None     EISSN: 22352988     Source Type: Journal    
DOI: 10.3389/fcimb.2017.00160     Document Type: Review

References (95)

1. Aarbiou, J., Tjabringa, G. S., Verhoosel, R. M., Ninaber, D. K., White, S. R., Peltenburg, L. T. C., et al. (2006). Mechanisms of cell death induced by the neutrophil antimicrobial peptides a-defensins and LL-37. Inflamm. Res. 55, 119-127. doi: 10.1007/s00011-005-0062-9
2. Actor, J. K., Hwang, S.-A., Olsen, M., Zimecki, M., Hunter, R. L., and Kruzel, M. L. (2002). Lactoferrin immunomodulation of DTH response in mice. Int. Immunopharmacol. 2, 475-486. doi: 10.1016/S1567-5769(01)00189-8
3. Ashitani, J.-I., Mukae, H., Arimura, Y., Sano, A., Tokojima, M., and Nakazato, M. (2004). High concentrations of alpha-defensins in plasma and bronchoalveolar lavage fluid of patients with acute respiratory distress syndrome. Life Sci. 75, 1123-1134. doi: 10.1016/j.lfs.2004.01.028
4. Auten, R. L., Mason, S. N., Tanaka, D. T., Welty-Wolf, K., and Whorton, M. H. (2001). Anti-neutrophil chemokine preserves alveolar development in hyperoxia-exposed newborn rats. Am. J. Physiol. Lung Cell Mol. Physiol. 281, L336-L344
5. Auten, R. L., Whorton, M. H., and Nicholas Mason, S. (2002). Blocking neutrophil influx reduces DNA damage in hyperoxia-exposed newborn rat lung. Am. J. Respir. Cell Mol. Biol. 26, 391-397. doi: 10.1165/ajrcmb.26.4.4708
6. Bainton, D. F., and Farquhar, M. G. (1968a). Differences in enzyme content of azurophil and specific granules of polymorphonuclear leukocytes. I. Histochemical staining of bone marrow smears. J. Cell Biol. 39, 286-298. doi: 10.1083/jcb.39.2.286
7. Bainton, D. F., and Farquhar, M. G. (1968b). Differences in enzyme content of azurophil and specific granules of polymorphonuclear leukocytes. II. Cytochemistry and electron microscopy of bone marrow cells. J. Cell Biol. 39, 299-317. doi: 10.1083/jcb.39.2.299
8. Barlow, P. G., Li, Y., Wilkinson, T. S., Bowdish, D. M. E., Lau, Y. E., Cosseau, C., et al. (2006). The human cationic host defense peptide LL-37 mediates contrasting effects on apoptotic pathways in different primary cells of the innate immune system. J. Leukoc. Biol. 80, 509-520. doi: 10.1189/jlb.1005560
9. Bdeir, K., Higazi, A. A.-R., Kulikovskaya, I., Christofidou-Solomidou, M., Vinogradov, S. A., Allen, T. C., et al. (2010). Neutrophil alpha-defensins cause lung injury by disrupting the capillary-epithelial barrier. Am. J. Respir. Crit. Care Med. 181, 935-946. doi: 10.1164/rccm.200907-1128OC
10. Beiter, K., Wartha, F., Albiger, B., Normark, S., Zychlinsky, A., and Henriques-Normark, B. (2006). An endonuclease allows Streptococcus pneumoniae to escape from neutrophil extracellular traps. Curr. Biol. 16, 401-407. doi: 10.1016/j.cub.2006.01.056
11. Belaaouaj, A., Kim, K. S., and Shapiro, S. D. (2000). Degradation of outer membrane protein A in Escherichia coli killing by neutrophil elastase. Science 289, 1185-1188. doi: 10.1126/science.289.5482.1185
12. Belaaouaj, A., McCarthy, R., Baumann, M., Gao, Z., Ley, T. J., Abraham, S. N., et al. (1998). Mice lacking neutrophil elastase reveal impaired host defense against gram negative bacterial sepsis. Nat. Med. 4, 615-618. doi: 10.1038/nm0598-615
13. Bhowmick, R., Tin Maung, N. H., Hurley, B. P., Ghanem, E. B., Gronert, K., McCormick, B. A., et al. (2013). Systemic disease during Streptococcus pneumoniae acute lung infection requires 12-lipoxygenase-dependent inflammation. J. Immunol. 191, 5115-5123. doi: 10.4049/jimmunol.1300522
14. Bordon, J., Aliberti, S., Fernandez-Botran, R., Uriarte, S. M., Rane, M. J., Duvvuri, P., et al. (2013). Understanding the roles of cytokines and neutrophil activity and neutrophil apoptosis in the protective versus deleterious inflammatory response in pneumonia. Int. J. Infect. Dis. 17, e76-e83. doi: 10.1016/j.ijid.2012.06.006
15. Borregaard, N., Sørensen, O. E., and Theilgaard-Mönch, K. (2007). Neutrophil granules: a library of innate immunity proteins. Trends Immunol. 28, 340-345. doi: 10.1016/j.it.2007.06.002
16. Bou Ghanem, E. N., Clark, S., Roggensack, S. E., McIver, S. R., Alcaide, P., Haydon, P. G., et al. (2015). Extracellular adenosine protects against Streptococcus pneumoniae lung infection by regulating pulmonary neutrophil recruitment. PLoS Pathog. 11:e1005126. doi: 10.1371/journal.ppat.1005126
17. Boxio, R., Wartelle, J., Nawrocki-Raby, B., Lagrange, B., Malleret, L., Hirche, T., et al. (2016). Neutrophil elastase cleaves epithelial cadherin in acutely injured lung epithelium. Respir. Res. 17, 129. doi: 10.1186/s12931-016-0449-x
18. Brandes, M., Klauschen, F., Kuchen, S., and Germain, R. N. (2013). A systems analysis identifies a feedforward inflammatory circuit leading to lethal influenza infection. Cell 154, 197-212. doi: 10.1016/j.cell.2013.06.013
19. Brinkmann, V., Reichard, U., Goosmann, C., Fauler, B., Uhlemann, Y., Weiss, D. S., et al. (2004). Neutrophil extracellular traps kill bacteria. Science 303, 1532-1535. doi: 10.1126/science.1092385
20. Brinkmann, V., and Zychlinsky, A. (2007). Beneficial suicide: why neutrophils die to make NETs. Nat. Rev. Microbiol. 5, 577-582. doi: 10.1038/nrmicro1710
21. Chen, H.-C., Lin, H.-C., Liu, C.-Y., Wang, C.-H., Hwang, T., Huang, T.-T., et al. (2004). Neutrophil elastase induces IL-8 synthesis by lung epithelial cells via the mitogen-activated protein kinase pathway. J. Biomed. Sci. 11, 49-58. doi: 10.1007/BF02256548
22. Chiang, N., Fredman, G., Bäckhed, F., Oh, S. F., Vickery, T., Schmidt, B. A., et al. (2012). Infection regulates pro-resolving mediators that lower antibiotic requirements. Nature 484, 524-528. doi: 10.1038/nature11042
23. Cohen, T. S., Jones-Nelson, O., Hotz, M., Cheng, L., Miller, L. S., Suzich, J., et al. (2016). S. aureus blocks efferocytosis of neutrophils by macrophages through the activity of its virulence factor alpha toxin. Sci Rep 6:35466. doi: 10.1038/srep35466
24. Confalonieri, M., Urbino, R., Potena, A., Piattella, M., Parigi, P., Puccio, G., et al. (2005). Hydrocortisone infusion for severe community-acquired pneumonia: a preliminary randomized study. Am. J. Respir Crit. Care Med. 171, 242-248. doi: 10.1164/rccm.200406-808OC
25. Craig, A., Mai, J., Cai, S., and Jeyaseelan, S. (2009). Neutrophil recruitment to the lungs during bacterial pneumonia. Infect. Immun. 77, 568-575. doi: 10.1128/IAI.00832-08
26. Dinauer, M. C., Lekstrom-Himes, J. A., and Dale, D. C. (2000). Inherited neutrophil disorders: molecular basis and new therapies. Hematol. Am. Soc. Hematol. Educ. Progr. 2000, 303-318. doi: 10.1182/asheducation-2000.1.303
27. Doss, M., White, M. R., Tecle, T., and Hartshorn, K. L. (2010). Human defensins and LL-37 in mucosal immunity. J. Leukoc. Biol. 87, 79-92. doi: 10.1189/jlb.0609382
28. Fahy, R. J., and Wewers, M. D. (2005). Pulmonary defense and the human cathelicidin hCAP-18/LL-37. Immunol. Res. 31, 75-89. doi: 10.1385/IR:31:2:075
29. Galli, S. J., Borregaard, N., and Wynn, T. A. (2011). Phenotypic and functional plasticity of cells of innate immunity: macrophages, mast cells and neutrophils. Nat. Immunol. 12, 1035-1044. doi: 10.1038/ni.2109
30. Garvy, B. A., and Harmsen, A. G. (1996). The importance of neutrophils in resistance to pneumococcal pneumonia in adult and neonatal mice. Inflammation 20, 499-512. doi: 10.1007/BF01487042
31. Ginzberg, H. H., Cherapanov, V., Dong, Q., Cantin, A., McCulloch, C. A., Shannon, P. T., et al. (2001). Neutrophil-mediated epithelial injury during transmigration: role of elastase. Am. J. Physiol. Gastrointest. Liver Physiol. 281, G705-G717
32. Gomez, J. C., Wang, Q., and Doerschuk, C. M. (2012). Neutrophils in Acute Bacterial Pneumonia. New York, NY: Springer
33. Good, R. A., Quie, P. G., Windhorst, D. B., Page, A. R., Rodey, G. E., White, J., et al. (1968). Fatal (chronic) granulomatous disease of childhood: a hereditary defect of leukocyte function. Semin. Hematol. 5, 215-254
34. Grommes, J., and Soehnlein, O. (2011). Contribution of neutrophils to acute lung injury. Mol. Med. 17, 1. doi: 10.2119/molmed.2010.00138
35. Hahn, I., Klaus, A., Janze, A.-K., Steinwede, K., Ding, N., Bohling, J., et al. (2011). Cathepsin G and neutrophil elastase play critical and nonredundant roles in lung-protective immunity against Streptococcus pneumoniae in mice. Infect. Immun. 79, 4893-4901. doi: 10.1128/IAI.05593-11
36. Hampton, M. B., Kettle, A. J., and Winterbourn, C. C. (1998). Inside the neutrophil phagosome: oxidants, myeloperoxidase, and bacterial killing. Blood 92, 3007-3017
37. Ichikawa, A., Kuba, K., Morita, M., Chida, S., Tezuka, H., Hara, H., et al. (2013). CXCL10-CXCR3 enhances the development of neutrophil-mediated fulminant lung injury of viral and nonviral origin. Am. J. Respir Crit. Care Med. 187, 65-77. doi: 10.1164/rccm.201203-0508OC
38. Jeyaseelan, S., Chu, H. W., Young, S. K., and Worthen, G. S. (2004). Transcriptional profiling of lipopolysaccharide-induced acute lung injury. Infect. Immun. 72, 7247-7256. doi: 10.1128/IAI.72.12.7247-7256.2004
39. Jeyaseelan, S., Manzer, R., Young, S. K., Yamamoto, M., Akira, S., Mason, R. J., et al. (2005). Induction of CXCL5 during inflammation in the rodent lung involves activation of alveolar epithelium. Am. J. Respir. Cell Mol. Biol. 32, 531-539. doi: 10.1165/rcmb.2005-0063OC
40. Jeyaseelan, S., Young, S. K., Yamamoto, M., Arndt, P. G., Akira, S., Kolls, J. K., et al. (2006). Toll/IL-1R domain-containing adaptor protein (TIRAP) is a critical mediator of antibacterial defense in the lung against Klebsiella pneumoniae but not Pseudomonas aeruginosa. J. Immunol. 177, 538-547. doi: 10.4049/jimmunol.177.1.538
41. Johnson, K. J., Fantone, J. C., Kaplan, J., and Ward, P. A. (1981). In vivo damage of rat lungs by oxygen metabolites. J. Clin. Invest. 67, 983-993. doi: 10.1172/JCI110149
42. Kai-Larsen, Y., and Agerberth, B. (2008). The role of the multifunctional peptide LL-37 in host defense. Front. Biosci. 13, 3760-3767. doi: 10.2741/2964
43. Kawabata, K., Hagio, T., Matsumoto, S., Nakao, S., Orita, S., Aze, Y., et al. (2000). Delayed neutrophil elastase inhibition prevents subsequent progression of acute lung injury induced by endotoxin inhalation in hamsters. Am. J. Respir Crit. Care Med. 161, 2013-2018. doi: 10.1164/ajrccm.161.6.9904047
44. Klebanoff, S. J. (2005). Myeloperoxidase: friend and foe. J. Leukoc. Biol. 77, 598-625. doi: 10.1189/jlb.1204697
45. Kolaczkowska, E., and Kubes, P. (2013). Neutrophil recruitment and function in health and inflammation. Nat. Rev. Immunol. 13, 159-175. doi: 10.1038/nri3399
46. Korkmaz, B., Horwitz, M. S., Jenne, D. E., and Gauthier, F. (2010). Neutrophil elastase, proteinase 3, and cathepsin G as therapeutic targets in human diseases. Pharmacol. Rev. 62, 726-759. doi: 10.1124/pr.110.002733
47. Kreisel, D., Nava, R. G., Li, W., Zinselmeyer, B. H., Wang, B., Lai, J., et al. (2010). In vivo two-photon imaging reveals monocyte-dependent neutrophil extravasation during pulmonary inflammation. Proc. Natl. Acad. Sci. U.S.A. 107, 18073-18078. doi: 10.1073/pnas.1008737107
48. Lee, W. L., and Downey, G. P. (2001). Neutrophil activation and acute lung injury. Curr. Opin. Crit. Care 7, 1-7. doi: 10.1097/00075198-200102000-00001
49. Levay, P. F., and Viljoen, M. (1995). Lactoferrin: a general review. Haematologica 80, 252-267
50. Levine, A. P., and Segal, A. W. (2016). The NADPH oxidase and microbial killing by neutrophils, with a particular emphasis on the proposed antimicrobial role of myeloperoxidase within the phagocytic vacuole. Microbiol. Spectr. 4. doi: 10.1128/microbiolspec.MCHD-0018-2015
51. Liou, T. G., and Campbell, E. J. (1995). Nonisotropic enzyme-inhibitor interactions: a novel nonoxidative mechanism for quantum proteolysis by human neutrophils. Biochemistry 34, 16171-16177. doi: 10.1021/bi00049a032
52. Martin, T. R. (2002). Neutrophils and lung injury: getting it right. J. Clin. Invest. 110, 1603-1605. doi: 10.1172/JCI0217302
53. Mei, J., Liu, Y., Dai, N., Favara, M., Greene, T., Jeyaseelan, S., et al. (2010). CXCL5 regulates chemokine scavenging and pulmonary host defense to bacterial infection. Immunity 33, 106-117. doi: 10.1016/j.immuni.2010.07.009
54. Meng, W., Paunel-Görgülü, A., Flohé, S., Hoffmann, A., Witte, I., MacKenzie, C., et al. (2012). Depletion of neutrophil extracellular traps in vivo results in hypersusceptibility to polymicrobial sepsis in mice. Crit Care 16, R137. doi: 10.1186/cc11442
55. Miles, K., Clarke, D. J., Lu, W., Sibinska, Z., Beaumont, P. E., Davidson, D. J., et al. (2009). Dying and necrotic neutrophils are anti-inflammatory secondary to the release of a-defensins. J. Immunol. 183, 2122-2132. doi: 10.4049/jimmunol.0804187
56. Mizgerd, J. P. (2006). Lung infection-a public health priority. PLoS Med. 3:e76. doi: 10.1371/journal.pmed.0030076
57. Mizgerd, J. P. (2008). Acute lower respiratory tract infection. N. Engl. J. Med. 358, 716-727. doi: 10.1056/NEJMra074111
58. Mizgerd, J. P. (2012). Respiratory infection and the impact of pulmonary immunity on lung health and disease. Am. J. Respir Crit. Care Med. 186, 824-829. doi: 10.1164/rccm.201206-1063PP
59. Moorthy, A. N., Rai, P., Jiao, H., Wang, S., Tan, K. B., Qin, L., et al. (2016). Capsules of virulent pneumococcal serotypes enhance formation of neutrophil extracellular traps during in vivo pathogenesis of pneumonia. Oncotarget 7, 19327-19340. doi: 10.18632/oncotarget.8451
60. Moraes, T. J., Zurawska, J. H., and Downey, G. P. (2006). Neutrophil granule contents in the pathogenesis of lung injury. Curr. Opin. Hematol. 13, 21-27. doi: 10.1097/01.moh.0000190113.31027.d5
61. Müller, I., Munder, M., Kropf, P., and Hänsch, G. M. (2009). Polymorphonuclear neutrophils and T lymphocytes: strange bedfellows or brothers in arms? Trends Immunol. 30, 522-530. doi: 10.1016/j.it.2009.07.007
62. Narasaraju, T., Yang, E., Samy, R. P., Ng, H. H., Poh, W. P., Liew, A.-A., et al. (2011). Excessive neutrophils and neutrophil extracellular traps contribute to acute lung injury of influenza pneumonitis. Am. J. Pathol. 179, 199-210. doi: 10.1016/j.ajpath.2011.03.013
63. Nathan, C. (2006). Neutrophils and immunity: challenges and opportunities. Nat. Publ. Group 6, 173-182. doi: 10.1038/nri1785
64. Nathan, C., and Ding, A. (2010). Nonresolving inflammation. Cell 140, 871-882. doi: 10.1016/j.cell.2010.02.029
65. Osman, M. O., Kristensen, J. U., Jacobsen, N. O., Lausten, S. B., Deleuran, B., Deleuran, M., et al. (1998). A monoclonal anti-interleukin 8 antibody (WS-4) inhibits cytokine response and acute lung injury in experimental severe acute necrotising pancreatitis in rabbits. Gut 43, 232-239. doi: 10.1136/gut.43.2.232
66. Papayannopoulos, V., Metzler, K. D., Hakkim, A., and Zychlinsky, A. (2010). Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps. J. Cell Biol. 191, 677-691. doi: 10.1083/jcb.201006052
67. Pechous, R. D., Broberg, C. A., Stasulli, N. M., Miller, V. L., and Goldman, W. E. (2015). In vivo transcriptional profiling of Yersinia pestis reveals a novel bacterial mediator of pulmonary inflammation. MBio 6, e02302-14. doi: 10.1128/mBio.02302-14
68. Pechous, R. D., Sivaraman, V., Price, P. A., Stasulli, N. M., and Goldman, W. E. (2013). Early host cell targets of Yersinia pestis during primary pneumonic plague. PLoS Pathog. 9:e1003679. doi: 10.1371/journal.ppat.1003679
69. Pham, C. T. N. (2006). Neutrophil serine proteases: specific regulators of inflammation. Nat. Publ. Group 6, 541-550. doi: 10.1038/nri1841
70. Porto, B. N., and Stein, R. T. (2016). Neutrophil extracellular traps in pulmonary diseases: too much of a good thing? Front. Immunol. 7:311. doi: 10.3389/fimmu.2016.00311
71. Quinton, L. J., and Mizgerd, J. P. (2015). Dynamics of lung defense in pneumonia: resistance, resilience, and remodeling. Annu. Rev. Physiol. 77, 407-430. doi: 10.1146/annurev-physiol-021014-071937
72. Reeves, E. P., Lu, H., Jacobs, H. L., Messina, C. G. M., Bolsover, S., Gabella, G., et al. (2002). Killing activity of neutrophils is mediated through activation of proteases by K+ flux. Nature 416, 291-297. doi: 10.1038/416291a
73. Rendon, A., Rendon-Ramirez, E. J., and Rosas-Taraco, A. G. (2016). Relevant cytokines in the management of community-acquired pneumonia. Curr. Infect. Dis. Rep. 18, 10. doi: 10.1007/s11908-016-0516-y
74. Restrepo, M. I., and Anzueto, A. (2009). Severe community-acquired pneumonia. Infect. Dis. Clin. North Am. 23, 503-520. doi: 10.1016/j.idc.2009.04.003
75. Saffarzadeh, M., Juenemann, C., Queisser, M. A., Lochnit, G., Barreto, G., Galuska, S. P., et al. (2012). Neutrophil extracellular traps directly induce epithelial and endothelial cell death: a predominant role of histones. PLoS ONE 7:e32366. doi: 10.1371/journal.pone.0032366
76. Sahoo, M., Del Barrio, L., Miller, M. A., and Re, F. (2014). Neutrophil elastase causes tissue damage that decreases host tolerance to lung infection with burkholderia species. PLoS Pathog. 10:e1004327. doi: 10.1371/journal.ppat.1004327
77. Sakamoto, N., Mukae, H., Fujii, T., Ishii, H., Yoshioka, S., Kakugawa, T., et al. (2005). Differential effects of alpha-and beta-defensin on cytokine production by cultured human bronchial epithelial cells. Am. J. Physiol. Lung Cell Mol. Physiol. 288, L508-L513. doi: 10.1152/ajplung.00076.2004
78. Schreiber, A., Busjahn, A., Luft, F. C., and Kettritz, R. (2003). Membrane expression of proteinase 3 is genetically determined. J. Am. Soc. Nephrol. 14, 68-75. doi: 10.1097/01.ASN.0000040751.83734.D1
79. Serhan, C. N., Chiang, N., Dalli, J., and Levy, B. D. (2014). Lipid mediators in the resolution of inflammation. Cold Spring Harb. Perspect. Biol. 7:a016311. doi: 10.1101/cshperspect.a016311
80. Serhan, C. N., Hong, S., Gronert, K., Colgan, S. P., Devchand, P. R., Mirick, G., et al. (2002). Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals. J. Exp. Med. 196, 1025-1037. doi: 10.1084/jem.20020760
81. Smart, S. J., and Casale, T. B. (1994a). Pulmonary epithelial cells facilitate TNF-alpha-induced neutrophil chemotaxis. A role for cytokine networking. J. Immunol. 152, 4087-4094
82. Smart, S. J., and Casale, T. B. (1994b). TNF-alpha-induced transendothelial neutrophil migration is IL-8 dependent. Am. J. Physiol. 266, L238-L245
83. Soehnlein, O., Oehmcke, S., Ma, X., Rothfuchs, A. G., Frithiof, R., Van Rooijen, N., et al. (2008). Neutrophil degranulation mediates severe lung damage triggered by streptococcal M1 protein. Eur. Respir. J. 32, 405-412. doi: 10.1183/09031936.00173207
84. Standish, A. J., and Weiser, J. N. (2009). Human neutrophils kill Streptococcus pneumoniae via serine proteases. J. Immunol. 183, 2602-2609. doi: 10.4049/jimmunol.0900688
85. Stasulli, N. M., Eichelberger, K. R., Price, P. A., Pechous, R. D., Montgomery, S. A., Parker, J. S., et al. (2015). Spatially distinct neutrophil responses within the inflammatory lesions of pneumonic plague. MBio. 6:e01530-15. doi: 10.1128/mBio.01530-15
86. Suzuki, T., Yamashita, C., Zemans, R. L., Briones, N., Van Linden, A., and Downey, G. P. (2009). Leukocyte elastase induces lung epithelial apoptosis via a PAR-1-, NF-κB-, and p53-dependent pathway. Am. J. Respir. Cell Mol. Biol. 41, 742-755. doi: 10.1165/rcmb.2008-0157OC
87. Tateda, K., Moore, T. A., Deng, J. C., Newstead, M. W., Zeng, X., Matsukawa, A., et al. (2001). Early recruitment of neutrophils determines subsequent T1/T2 host responses in a murine model of Legionella pneumophila pneumonia. J. Immunol. 166, 3355-3361. doi: 10.4049/jimmunol.166.5.3355
88. Tkalcevic, J., Novelli, M., Phylactides, M., Iredale, J. P., Segal, A. W., and Roes, J. (2000). Impaired immunity and enhanced resistance to endotoxin in the absence of neutrophil elastase and cathepsin G. Immunity 12, 201-210. doi: 10.1016/S1074-7613(00)80173-9
89. Usatyuk, P. V., and Natarajan, V. (2005). Regulation of reactive oxygen species-induced endothelial cell-cell and cell-matrix contacts by focal adhesion kinase and adherens junction proteins. Am. J. Physiol. Lung Cell Mol. Physiol. 289, L999-L1010. doi: 10.1152/ajplung.00211.2005
90. Vandivier, R. W., Fadok, V. A., Hoffmann, P. R., Bratton, D. L., Penvari, C., Brown, K. K., et al. (2002). Elastase-mediated phosphatidylserine receptor cleavage impairs apoptotic cell clearance in cystic fibrosis and bronchiectasis. J. Clin. Invest. 109, 661-670. doi: 10.1172/JCI0213572
91. Wang, W., Suzuki, Y., Tanigaki, T., Rank, D. R., and Raffin, T. A. (1994). Effect of the NADPH oxidase inhibitor apocynin on septic lung injury in guinea pigs. Am. J. Respir. Crit. Care Med. 150, 1449-1452. doi: 10.1164/ajrccm.150.5.7952574
92. Wartha, F., Beiter, K., Albiger, B., Fernebro, J., Zychlinsky, A., Normark, S., et al. (2007). Capsule and D-alanylated lipoteichoic acids protect Streptococcus pneumoniae against neutrophil extracellular traps. Cell Microbiol. 9, 1162-1171. doi: 10.1111/j.1462-5822.2006.00857.x
93. Weinrauch, Y., Drujan, D., Shapiro, S. D., Weiss, J., and Zychlinsky, A. (2002). Neutrophil elastase targets virulence factors of enterobacteria. Nature 417, 91-94. doi: 10.1038/417091a
94. Witherden, I. R., Vanden Bon, E. J., Goldstraw, P., Ratcliffe, C., Pastorino, U., and Tetley, T. D. (2004). Primary human alveolar type II epithelial cell chemokine release: effects of cigarette smoke and neutrophil elastase. Am. J. Respir. Cell Mol. Biol. 30, 500-509. doi: 10.1165/rcmb.4890
95. Yamada, K., Yanagihara, K., Araki, N., Harada, Y., Morinaga, Y., Izumikawa, K., et al. (2011). In vivo efficacy of KRP-109, a novel elastase inhibitor, in a murine model of severe pneumococcal pneumonia. Pulm. Pharmacol. Ther. 24, 660-665. doi: 10.1016/j.pupt.2011.08.001