Serine Protease Cathepsin G Regulates Adhesion-Dependent Neutrophil Effector Functions by Modulating Integrin Clustering

The polymorphonuclear leukocyte (PMN)-derived serine proteases play a key role in immune complex (IC)-mediated inflammation. However, the mechanisms by which these proteases regulate inflammatory response remain largely undefined. Here, we show that IC-activated cathepsin G- and neutrophil elastase-...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2005-06, Vol.22 (6), p.679-691
Main Authors: Raptis, Sofia Z., Shapiro, Steven D., Simmons, Pamela M., Cheng, Alec M., Pham, Christine T.N.
Format: Article
Language:English
Subjects:
Adhesion
Animals
Antigen-Antibody Complex - immunology
Arthritis
Autoimmune diseases
Blotting, Western
Cathepsin G
Cathepsins - immunology
Cathepsins - metabolism
Cell Adhesion - physiology
Cell culture
Cells, Cultured
Chemokines
Chemokines - biosynthesis
Humans
Immune system
Integrins - physiology
Leukocyte Elastase - metabolism
Leukocytes
Mice
Neutrophils - physiology
Reactive Oxygen Species - metabolism
Recruitment
Respiratory Burst - physiology
Serine Endopeptidases - immunology
Serine Endopeptidases - metabolism
Studies
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Summary:The polymorphonuclear leukocyte (PMN)-derived serine proteases play a key role in immune complex (IC)-mediated inflammation. However, the mechanisms by which these proteases regulate inflammatory response remain largely undefined. Here, we show that IC-activated cathepsin G- and neutrophil elastase-deficient (CG/NE) PMNs adhered normally to IC-coated surfaces but did not undergo CD11b clustering and failed to initiate cytoskeletal reorganization and cell spreading. As a result, CG/NE-deficient PMNs exhibited severe defects in MIP-2 secretion and reactive oxygen intermediates production. Exogenously added CG, but not proteolytically inactive CG, was sufficient to restore these defects. These findings identify an important role for CG in integrin-dependent PMN effector functions that are separate from and downstream of integrin-dependent adhesion.
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2005.03.015