Lack of neutrophil elastase reduces inflammation, mucus hypersecretion, and emphysema, but not mucus obstruction, in mice with cystic fibrosislike lung disease

American Journal of Respiratory and Critical Care Medicine

Volumn 189, Issue 9, 2014, Pages 1082-1092

  Gehrig, Stefanie ^a,b,c   Duerr, Julia ^a,b   Weitnauer, Michael ^a   Wagner, Claudius J ^a,b   Graeber, Simon Y ^a,b   Schatterny, Jolanthe ^a,b   Hirtz, Stephanie ^a,b   Belaaouaj, Abderrazzaq ^d   Dalpke, Alexander H ^a,b   Schultz, Carsten ^a,b,c   Mall, Marcus A ^a,b  

^a UNIVERSITY OF HEIDELBERG   (Germany)

^b German Center for Lung Research   (Germany)

^c EUROPEAN MOLECULAR BIOLOGY LABORATORY   (Germany)

^d CENTRE HOSPITALIER LYON SUD   (France)

Author keywords

Airway inflammation; Cystic fibrosis; FRET reporter; Mucin hypersecretion; Neutrophilic airway disease

Indexed keywords

LEUKOCYTE ELASTASE; MUCIN; EPITHELIAL SODIUM CHANNEL; SCNN1B PROTEIN, MOUSE;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BACTERIAL INFECTION; CLINICAL ARTICLE; CONTROLLED STUDY; CYSTIC FIBROSIS; FLUORESCENCE RESONANCE ENERGY TRANSFER; GENE DELETION; GENE EXPRESSION; GOBLET CELL; HUMAN; IN VIVO STUDY; LUNG DISEASE; LUNG EMPHYSEMA; LUNG INJURY; LUNG LAVAGE; LUNG VOLUME; METAPLASIA; MORTALITY; MOUSE; MUCUS SECRETION; NEUTROPHIL; NEUTROPHILIA; NONHUMAN; PATHOGENESIS; PHENOTYPE; PRIORITY JOURNAL; REAL TIME POLYMERASE CHAIN REACTION; RESPIRATORY TRACT INFLAMMATION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SPUTUM ANALYSIS; AIRWAY OBSTRUCTION; ANIMAL; BRONCHIECTASIS; DISEASE MODEL; GENETICS; INFLAMMATION; KAPLAN MEIER METHOD; LUNG; MICROBIOLOGY; MUCUS; PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY; SECRETION (PROCESS); SPUTUM;

AIRWAY OBSTRUCTION; ANIMALS; BRONCHIECTASIS; CYSTIC FIBROSIS; DISEASE MODELS, ANIMAL; EPITHELIAL SODIUM CHANNELS; GENE DELETION; HUMANS; INFLAMMATION; KAPLAN-MEIER ESTIMATE; LEUKOCYTE ELASTASE; LUNG; MICE; MUCUS; REAL-TIME POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; SPUTUM;

EID: 84899791723     PISSN: 1073449X     EISSN: 15354970     Source Type: Journal    
DOI: 10.1164/rccm.201311-1932OC     Document Type: Article

References (58)

1. Sly PD, Brennan S, Gangell C, de Klerk N, Murray C, Mott L, Stick SM, Robinson PJ, Robertson CF, Ranganathan SC; Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST-CF). Lung disease at diagnosis in infants with cystic fibrosis detected by newborn screening. Am J Respir Crit Care Med 2009;180:146-152.
2. Sly PD, Gangell CL, Chen L, Ware RS, Ranganathan S, Mott LS, Murray CP, Stick SM; AREST CF Investigators. Risk factors for bronchiectasis in children with cystic fibrosis. N Engl J Med 2013;368:1963-1970.
3. Grasemann H, Ratjen F. Early lung disease in cystic fibrosis. Lancet Respir Med 2013;1:148-157.
4. 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;186:857-865.
5. Voynow JA, Fischer BM, Zheng S. Proteases and cystic fibrosis. Int J Biochem Cell Biol 2008;40:1238-1245.
6. Owen CA. Roles for proteinases in the pathogenesis of chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 2008;3:253-268.
7. Pham CT. Neutrophil serine proteases: specific regulators of inflammation. Nat Rev Immunol 2006;6:541-550.
8. Lee WL, Downey GP. Leukocyte elastase: physiological functions and role in acute lung injury. Am J Respir Crit Care Med 2001;164: 896-904.
9. Fahy JV, Dickey BF. Airway mucus function and dysfunction. N Engl J Med 2010;363:2233-2247.
10. Gibson RL, Burns JL, Ramsey BW. Pathophysiology and management of pulmonary infections in cystic fibrosis. Am J Respir Crit Care Med 2003;168:918-951.
11. Taggart CC, Greene CM, Carroll TP, O'Neill SJ, McElvaney NG. Elastolytic proteases: inflammation resolution and dysregulation in chronic infective lung disease. Am J Respir Crit Care Med 2005;171: 1070-1076.
12. Le Gars M, Descamps D, Roussel D, Saussereau E, Guillot L, Ruffin M, Tabary O, Hong SS, Boulanger P, Paulais M, et al. Neutrophil elastase degrades cystic fibrosis transmembrane conductance regulator via calpains and disables channel function in vitro and in vivo. Am J Respir Crit Care Med 2013;187:170-179.
13. Caldwell RA, Boucher RC, Stutts MJ. Neutrophil elastase activates near-silent epithelial Na1 channels and increases airway epithelial Na 1 transport. Am J Physiol Lung Cell Mol Physiol 2005;288:L813-L819.
14. Mall M.A. Role of the amiloride-sensitive epithelial Na1 channel in the pathogenesis and as a therapeutic target for cystic fibrosis lung disease. Exp Physiol 2009;94:171-174.
15. Belaaouaj A, McCarthy R, Baumann M, Gao Z, Ley TJ, Abraham SN, Shapiro SD. Mice lacking neutrophil elastase reveal impaired host defense against gram negative bacterial sepsis. Nat Med 1998;4: 615-618.
16. Hirche TO, Benabid R, Deslee G, Gangloff S, Achilefu S, Guenounou M, Lebargy F, Hancock RE, Belaaouaj A. Neutrophil elastase mediates innate host protection against Pseudomonas aeruginosa. J Immunol 2008;181:4945-4954.
17. Boucher RC. Airway surface dehydration in cystic fibrosis: pathogenesis and therapy. Annu Rev Med 2007;58:157-170.
18. Mall M.A. Role of cilia, mucus, and airway surface liquid in mucociliary dysfunction: lessons from mouse models. J Aerosol Med Pulm Drug Deliv 2008;21:13-24.
19. Mall M, Grubb BR, Harkema JR, O'Neal WK, Boucher RC. Increased airway epithelial Na1 absorption produces cystic fibrosis-like lung disease in mice. Nat Med 2004;10:487-493.
20. Mall MA, Harkema JR, Trojanek JB, Treis D, Livraghi A, Schubert S, Zhou Z, Kreda SM, Tilley SL, Hudson EJ, et al. Development of chronic bronchitis and emphysema in b-epithelial Na1 channel-overexpressing mice. Am J Respir Crit Care Med 2008;177: 730-742.
21. Wielpütz MO, Eichinger M, Zhou Z, Leotta K, Hirtz S, Bartling SH, Semmler W, Kauczor HU, Puderbach M, Mall M.A. In vivo monitoring of cystic fibrosis-like lung disease in mice by volumetric computed tomography. Eur Respir J 2011;38:1060-1070.
22. Zhou Z, Duerr J, Johannesson B, Schubert SC, Treis D, Harm M, Graeber SY, Dalpke A, Schultz C, Mall M.A. The ENaC-overexpressing mouse as a model of cystic fibrosis lung disease. J Cyst Fibros 2011;10:S172-S182.
23. Livraghi-Butrico A, Kelly EJ, Klem ER, Dang H, Wolfgang MC, Boucher RC, Randell SH, O'Neal WK. Mucus clearance, MyD88-dependent and MyD88-independent immunity modulate lung susceptibility to spontaneous bacterial infection and inflammation. Mucosal Immunol 2012;5:397-408.
24. Mall MA, Graeber SY, Stahl M, Zhou-Suckow Z. Early cystic fibrosis lung disease: Role of airway surface dehydration and lessons from preventive rehydration therapies in mice. Int J Biochem Cell Biol (In press)
25. Gehrig S, Mall MA, Schultz C. Spatially resolved monitoring of neutrophil elastase activity with ratiometric fluorescent reporters. Angew Chem Int Ed Engl 2012;51:6258-6261.
26. Hu HY, Gehrig S, Reither G, Subramanian D, Mall MA, Plettenburg O, Schultz C. FRET-based and other fluorescent proteinase probes. Biotechnol J 2014;9:266-281.
27. Gehrig S, Dalpke A, Schultz C, Mall M.A. Neutrophil elastase modulates neutrophilic inflammation, goblet cell metaplasia and emphysema in chronic obstructive lung disease of bENaC-overexpressing mice [abstract]. Am J Respir Crit Care Med 2013;187:A3491.
28. Johannesson B, Hirtz S, Schatterny J, Schultz C, Mall M.A. CFTR regulates early pathogenesis of chronic obstructive lung disease in bENaC-overexpressing mice. PLoS ONE 2012;7:e44059.
29. Anagnostopoulou P, Dai L, Schatterny J, Hirtz S, Duerr J, Mall M.A. Allergic airway inflammation induces a pro-secretory epithelial ion transport phenotype in mice. Eur Respir J 2010;36:1436-1447.
30. Saetta M, Shiner RJ, Angus GE, Kim WD, Wang NS, King M, Ghezzo H, Cosio MG. Destructive index: a measurement of lung parenchymal destruction in smokers. Am Rev Respir Dis 1985;131:764-769.
31. Hector A, Jonas F, Kappler M, Feilcke M, Hartl D, Griese M. Novel method to process cystic fibrosis sputum for determination of oxidative state. Respiration 2010;80:393-400.
32. Cobos-Correa A, Trojanek JB, Diemer S, Mall MA, Schultz C. Membrane-bound FRET probe visualizes MMP12 activity in pulmonary inflammation. Nat Chem Biol 2009;5:628-630.
33. Kirchner KK, Wagener JS, Khan TZ, Copenhaver SC, Accurso FJ. Increased DNA levels in bronchoalveolar lavage fluid obtained from infants with cystic fibrosis. Am J Respir Crit Care Med 1996;154: 1426-1429.
34. Voynow JA, Fischer BM, Malarkey DE, Burch LH, Wong T, Longphre M, Ho SB, Foster WM. Neutrophil elastase induces mucus cell metaplasia in mouse lung. Am J Physiol Lung Cell Mol Physiol 2004; 287:L1293-L1302.
35. Voynow JA, Young LR, Wang Y, Horger T, Rose MC, Fischer BM. Neutrophil elastase increases MUC5AC mRNA and protein expression in respiratory epithelial cells. Am J Physiol 1999;276:L835-L843.
36. Shak S, Capon DJ, Hellmiss R, Marsters SA, Baker CL. Recombinant human DNase I reduces the viscosity of cystic fibrosis sputum. Proc Natl Acad Sci USA 1990;87:9188-9192.
37. Shapiro SD, Goldstein NM, Houghton AM, Kobayashi DK, Kelley D, Belaaouaj A. Neutrophil elastase contributes to cigarette smoke-induced emphysema in mice. Am J Pathol 2003;163:2329-2335.
38. Mayer-Hamblett N, Aitken ML, Accurso FJ, Kronmal RA, Konstan MW, Burns JL, Sagel SD, Ramsey BW. Association between pulmonary function and sputum biomarkers in cystic fibrosis. Am J Respir Crit Care Med 2007;175:822-828.
39. Owen CA, Campbell MA, Sannes PL, Boukedes SS, Campbell EJ. Cell surface-bound elastase and cathepsin G on human neutrophils: a novel, non-oxidative mechanism by which neutrophils focus and preserve catalytic activity of serine proteinases. J Cell Biol 1995;131: 775-789.
40. Hirche TO, Atkinson JJ, Bahr S, Belaaouaj A. Deficiency in neutrophil elastase does not impair neutrophil recruitment to inflamed sites. Am J Respir Cell Mol Biol 2004;30:576-584.
41. Diakov A, Bera K, Mokrushina M, Krueger B, Korbmacher C. Cleavage in the g-subunit of the epithelial sodium channel (ENaC) plays an important role in the proteolytic activation of near-silent channels. J Physiol 2008;586:4587-4608.
42. Mall MA, Button B, Johannesson B, Zhou Z, Livraghi A, Caldwell RA, Schubert SC, Schultz C, O'Neal WK, Pradervand S, et al. Airway surface liquid volume regulation determines different airway phenotypes in liddle compared with betaENaC-overexpressing mice. J Biol Chem 2010;285:26945-26955.
43. Fyfe GK, Canessa CM. Subunit composition determines the single channel kinetics of the epithelial sodium channel. J Gen Physiol 1998;112:423-432.
44. Button B, Cai LH, Ehre C, Kesimer M, Hill DB, Sheehan JK, Boucher RC, Rubinstein M. A periciliary brush promotes the lung health by separating the mucus layer from airway epithelia. Science 2012;337: 937-941.
45. Anagnostopoulou P, Riederer B, Duerr J, Michel S, Binia A, Agrawal R, Liu X, Kalitzki K, Xiao F, Chen M, et al. SLC26A9-mediated chloride secretion prevents mucus obstruction in airway inflammation. J Clin Invest 2012;122:3629-3634.
46. Graeber SY, Zhou-Suckow Z, Schatterny J, Hirtz S, Boucher RC, Mall M.A. Hypertonic saline is effective in the prevention and treatment of mucus obstruction, but not airway inflammation, in mice with chronic obstructive lung disease. Am J Respir Cell Mol Biol 2013;49: 410-417.
47. Becq F, Mall MA, Sheppard DN, Conese M, Zegarra-Moran O. Pharmacological therapy for cystic fibrosis: from bench to bedside. J Cyst Fibros 2011;10:S129-S145.
48. Zhou Z, Treis D, Schubert SC, Harm M, Schatterny J, Hirtz S, Duerr J, Boucher RC, Mall M.A. Preventive but not late amiloride therapy reduces morbidity and mortality of lung disease in betaENaC-overexpressing mice. Am J Respir Crit Care Med 2008;178:1245-1256.
49. Hartl D, Latzin P, Hordijk P, Marcos V, Rudolph C, Woischnik M, Krauss-Etschmann S, Koller B, Reinhardt D, Roscher AA, et al. Cleavage of CXCR1 on neutrophils disables bacterial killing in cystic fibrosis lung disease. Nat Med 2007;13:1423-1430.
50. Tunney MM, Field TR, Moriarty TF, Patrick S, Doering G, Muhlebach MS, Wolfgang MC, Boucher R, Gilpin DF, McDowell A, et al. Detection of anaerobic bacteria in high numbers in sputum from patients with cystic fibrosis. Am J Respir Crit Care Med 2008;177: 995-1001.
51. Bals R, Weiner DJ, Wilson JM. The innate immune system in cystic fibrosis lung disease. J Clin Invest 1999;103:303-307.
52. Griese M, Kappler M, Gaggar A, Hartl D. Inhibition of airway proteases in cystic fibrosis lung disease. Eur Respir J 2008;32:783-795.
53. Elborn JS, Perrett J, Forsman-Semb K, Marks-Konczalik J, Gunawardena K, Entwistle N. Efficacy, safety and effect on biomarkers of AZD9668 in cystic fibrosis. Eur Respir J 2012;40: 969-976.
54. Groutas WC, Dou D, Alliston KR. Neutrophil elastase inhibitors. Expert Opin Ther Pat 2011;21:339-354.
55. Churg A, Wright JL. Proteases and emphysema. Curr Opin Pulm Med 2005;11:153-159.
56. Shapiro SD. Animal models for COPD. Chest 2000; 117(5, Suppl 1) 223S-227S.
57. Wielpütz MO, Puderbach M, Kopp-Schneider A, Stahl M, Fritzsching E, Sommerburg O, Ley S, Sumkauskaite M, Biederer J, Kauczor HU, et al. Magnetic resonance imaging detects changes in structure and perfusion, and response to therapy in early cystic fibrosis lung disease. Am J Respir Crit Care Med 2014;189: 956-965.
58. Korkmaz B, Poutrain P, Hazouard E, de Monte M, Attucci S, Gauthier FL. Competition between elastase and related proteases from human neutrophil for binding to alpha1-protease inhibitor. Am J Respir Cell Mol Biol 2005;32:553-559.