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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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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 Total
Citations: 2 6 8 3 8 11 4 5 11 5 8 4 3 4 3 14 9 14 6 8 4 3 1 1 145
Citation information
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Citations to this article in year 2010 (14)

Title and authors Publication Year
The adaptor molecule CARD9 is essential for tuberculosis control
A Dorhoi, C Desel, V Yeremeev, L Pradl, V Brinkmann, HJ Mollenkopf, K Hanke, O Gross, J Ruland, SH Kaufmann
Journal of Experimental Medicine 2010
Role of Apoptosis in Amplifying Inflammatory Responses in Lung Diseases
EP Schmidt, RM Tuder
Journal of cell death 2010
Sphingolipid-mediated Inhibition of Apoptotic Cell Clearance by Alveolar Macrophages*
DN Petrusca, Y Gu, JJ Adamowicz, NI Rush, WC Hubbard, PA Smith, EV Berdyshev, KG Birukov, CH Lee, RM Tuder, HL 3rd, RW Vandivier, I Petrache
The Journal of biological chemistry 2010
Mechanisms of failed apoptotic cell clearance by phagocyte subsets in cardiovascular disease
EB Thorp
Apoptosis 2010
The identification of markers of macrophage differentiation in PMA-stimulated THP-1 cells and monocyte-derived macrophages
M Daigneault, JA Preston, HM Marriott, MK Whyte, DH Dockrell
PloS one 2010
Antiproteases as therapeutics to target inflammation in cystic fibrosis
DJ Quinn, S Weldon, CC Taggart
The open respiratory medicine journal 2010
Human neutrophil elastase-mediated cleavage sites of MMP-9 and TIMP-1: implications to cystic fibrosis proteolytic dysfunction
PL Jackson, X Xu, L Wilson, NM Weathington, JP Clancy, JE Blalock, A Gaggar
Molecular Medicine 2010
Proline-Glycine-Proline (PGP) and High Mobility Group Box Protein-1 (HMGB1): Potential Mediators of Cystic Fibrosis Airway Inflammation
A Gaggar, SM Rowe, H Matthew, JE Blalock
The open respiratory medicine journal 2010
Clearance of apoptotic cells: implications in health and disease
MR Elliott, KS Ravichandran
The Journal of Cell Biology 2010
Isolation and characterization of microparticles in sputum from cystic fibrosis patients
C Porro, S Lepore, T Trotta, S Castellani, L Ratclif, A Battaglino, SD Gioia, MC Martínez, M Conese, AB Maffione
Respiratory Research 2010
Proinflammatory phenotype and increased caveolin-1 in alveolar macrophages with silenced CFTR mRNA
Y Xu, A Krause, H Hamai, BG Harvey, TS Worgall, S Worgall
PloS one 2010
Pharmacologically directed cell disposal: labeling damaged cells for phagocytosis as a strategy against acute pancreatitis
M Chvanov, OH Petersen, AV Tepikin
Molecular interventions 2010
Proline-Glycine-Proline (PGP) and High Mobility Group Box Protein-1 (HMGB1): Potential Mediators of Cystic Fibrosis Airway Inflammation
Gaggar A, Rowe SM, Matthew H, Blalock JE
The open respiratory medicine journal 2010
Antiproteases as Therapeutics to Target Inflammation in Cystic Fibrosis
Quinn DJ, Weldon S, Taggart CC
The open respiratory medicine journal 2010

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