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Citations to this article

Elastase-mediated phosphatidylserine receptor cleavage impairs apoptotic cell clearance in cystic fibrosis and bronchiectasis
R. William Vandivier, … , Frank J. Accurso, Peter M. Henson
R. William Vandivier, … , Frank J. Accurso, Peter M. Henson
Published March 1, 2002
Citation Information: J Clin Invest. 2002;109(5):661-670. https://doi.org/10.1172/JCI13572.
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Elastase-mediated phosphatidylserine receptor cleavage impairs apoptotic cell clearance in cystic fibrosis and bronchiectasis

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Abstract

Cystic fibrosis is characterized by an early and sustained influx of inflammatory cells into the airways and by release of proteases. Resolution of inflammation is normally associated with the orderly removal of dying apoptotic inflammatory cells through cell recognition receptors, such as the phosphatidylserine receptor, CD36, and αv integrins. Accordingly, removal of apoptotic inflammatory cells may be impaired in persistent inflammatory responses such as that seen in cystic fibrosis airways. Examination of sputa from cystic fibrosis and non–cystic fibrosis bronchiectasis patients demonstrated an abundance of apoptotic cells, in excess of that seen in patients with chronic bronchitis. In vitro, cystic fibrosis and bronchiectasis airway fluid directly inhibited apoptotic cell removal by alveolar macrophages in a neutrophil elastase-dependent manner, suggesting that elastase may impair apoptotic cell clearance in vivo. Flow cytometry demonstrated that neutrophil elastase cleaved the phosphatidylserine receptor, but not CD36 or CD32 (FcγRII). Cleavage of the phosphatidylserine receptor by neutrophil elastase specifically disrupted phagocytosis of apoptotic cells, implying a potential mechanism for delayed apoptotic cell clearance in vivo. Therefore, defective airway clearance of apoptotic cells in cystic fibrosis and bronchiectasis may be due to elastase-mediated cleavage of phosphatidylserine receptor on phagocytes and may contribute to ongoing airway inflammation.

Authors

R. William Vandivier, Valerie A. Fadok, Peter R. Hoffmann, Donna L. Bratton, Churee Penvari, Kevin K. Brown, Joseph D. Brain, Frank J. Accurso, Peter M. Henson

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Profound functional and signaling changes in viable inflammatory neutrophils homing to cystic fibrosis airways
R Tirouvanziam, Y Gernez, CK Conrad, RB Moss, I Schrijver, CE Dunn, ZA Davies, LA Herzenberg, LA Herzenberg
Proceedings of the National Academy of Sciences 2008
Neutrophil-related immunoinflammatory disturbance in steroid-overdosed ulcerative colitis patients
S Yoshiyama, C Miki, Y Okita, T Araki, K Uchida, M Kusunoki
Journal of Gastroenterology 2008
Alveolar macrophage phagocytosis is impaired in children with poorly controlled asthma
AM Fitzpatrick, F Holguin, WG Teague, LA Brown
Journal of Allergy and Clinical Immunology 2008
Secondary necrosis in multicellular animals: an outcome of apoptosis with pathogenic implications
MT Silva, A do Vale, NM dos Santos
Apoptosis 2008
Roles for proteinases in the pathogenesis of chronic obstructive pulmonary disease.
Owen CA
International journal of chronic obstructive pulmonary disease 2008
Subversion of a Lysosomal Pathway Regulating Neutrophil Apoptosis by a Major Bacterial Toxin, Pyocyanin
Prince LR, Bianchi SM, Vaughan KM, Bewley MA, Marriott HM, Walmsley SR, Taylor GW, Buttle DJ, Sabroe I, Dockrell DH, Whyte MK
Journal of immunology (Baltimore, Md. : 1950) 2008
High mobility group protein-1 inhibits phagocytosis of apoptotic neutrophils through binding to phosphatidylserine.
Liu G, Wang J, Park YJ, Tsuruta Y, Lorne EF, Zhao X, Abraham E
Journal of immunology (Baltimore, Md. : 1950) 2008
Chronic Inflammation in the Cystic Fibrosis Lung: Alterations in Inter- and Intracellular Signaling
D Nichols, J Chmiel, M Berger
Clinical Reviews in Allergy & Immunology 2007
Apoptosis in health and disease and modulation of apoptosis for therapy: An overview
N Singh
Indian Journal of Clinical Biochemistry 2007
Neutrophil serine proteases fine-tune the inflammatory response
CT Pham
The International Journal of Biochemistry & Cell Biology 2007
Neutrophil Elastase Converts Human Immature Dendritic Cells into Transforming Growth Factor-β1-Secreting Cells and Reduces Allostimulatory Ability
PC Maffia, SE Zittermann, ML Scimone, N Tateosian, N Amiano, D Guerrieri, V Lutzky, D Rosso, HE Romeo, VE Garcia, AC Issekutz, HE Chuluyan
The American Journal of Pathology 2007
The neutrophil serine protease inhibitor serpinb1 preserves lung defense functions in Pseudomonas aeruginosa infection
C Benarafa, GP Priebe, E Remold-O'Donnell
Journal of Experimental Medicine 2007
Blockade of Apoptosis as a Rational Therapeutic Strategy for the Treatment of Sepsis
Ayala A, Wesche-Soldato DE, Perl M, Lomas-Neira JL, Swan R, Chung CS
Novartis Foundation symposium 2007
State of the art. Apoptosis and cell homeostasis in chronic obstructive pulmonary disease
PM Henson, GP Cosgrove, RW Vandivier
Proceedings of the American Thoracic Society 2006
Cell death, remodeling, and repair in chronic obstructive pulmonary disease?
PM Henson, RW Vandivier, IS Douglas
Proceedings of the American Thoracic Society 2006
Role of apoptosis in the pathogenesis of COPD and pulmonary emphysema
IK Demedts, T Demoor, KR Bracke, GF Joos, GG Brusselle
Respiratory Research 2006
Attenuation of host defense function of lung phagocytes in young cystic fibrosis patients
NE Alexis, MS Muhlebach, DB Peden, TL Noah
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society 2006
High-dose oral N-acetylcysteine, a glutathione prodrug, modulates inflammation in cystic fibrosis
R Tirouvanziam, CK Conrad, T Bottiglieri, LA Herzenberg, RB Moss, LA Herzenberg
Proceedings of the National Academy of Sciences 2006
Inhibition of neutrophil elastase prevents the development of murine dextran sulfate sodium-induced colitis
Y Morohoshi, K Matsuoka, H Chinen, N Kamada, T Sato, T Hisamatsu, S Okamoto, N Inoue, H Takaishi, H Ogata, Y Iwao, T Hibi
Journal of Gastroenterology 2006
Neutrophil elastase in colitis: more than a marker of disease activity?
R Hokari, S Miura
Journal of Gastroenterology 2006
Apoptotic mechanisms in the pathogenesis of COPD.
Plataki M, Tzortzaki E, Rytila P, Demosthenes M, Koutsopoulos A, Siafakas NM
International journal of chronic obstructive pulmonary disease 2006
Proteinases and oxidants as targets in the treatment of chronic obstructive pulmonary disease
CA Owen
Proceedings of the American Thoracic Society 2005
Apoptosis of airway epithelial cells: human serum sensitive induction by the cathelicidin LL-37
YE Lau, DM Bowdish, C Cosseau, RE Hancock, DJ Davidson
American journal of respiratory cell and molecular biology 2005
Dual oxidase 1-dependent MUC5AC mucin expression in cultured human airway epithelial cells
MX Shao, JA Nadel
Proceedings of the National Academy of Sciences 2005
Neutrophil cell death, activation and bacterial infection in cystic fibrosis
AP Watt, J Courtney, J Moore, M Ennis, JS Elborn
Thorax 2005
The macrophage and the apoptotic cell: an innate immune interaction viewed simplistically?
CD Gregory, A Devitt
Immunology 2004
Neutrophil apoptosis, proinflammatory mediators and cell counts in bronchiectasis
AP Watt, V Brown, J Courtney, M Kelly, L Garske, JS Elborn, M Ennis
Thorax 2004
Phagocytosis of Necrotic Cells by Macrophages Is Phosphatidylserine Dependent and Does Not Induce Inflammatory Cytokine Production
G Brouckaert, M Kalai, DV Krysko, X Saelens, D Vercammen, M Ndlovu, G Haegeman, K D'Herde, P Vandenabeele
Molecular biology of the cell 2004
Fourteen-member macrolides promote the phosphatidylserine receptor-dependent phagocytosis of apoptotic neutrophils by alveolar macrophages
T Yamaryo, K Oishi, H Yoshimine, Y Tsuchihashi, K Matsushima, T Nagatake
Antimicrobial agents and chemotherapy 2003
The Role of the Macrophage in Apoptosis: Hunter, Gatherer, and Regulator
FJ Geske, J Monks, L Lehman, VA Fadok
International Journal of Hematology 2002

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