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-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.
Raptis
Sofia Z
SZ
Division of Rheumatology, Washington University School of Medicine, Saint Louis, Missouri 63110, USA.
Shapiro
Steven D
SD
Simmons
Pamela M
PM
Cheng
Alec M
AM
Pham
Christine T N
CT
D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology; D015153:Blotting, Western; D056649:Cathepsin G; D002403:Cathepsins / Q000276:immunology / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology*; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis; D006801:Humans; D016023:Integrins / Q000502:physiology*; D019272:Leukocyte Elastase / Q000378:metabolism; D051379:Mice; D009504:Neutrophils / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst / Q000502:physiology; D012697:Serine Endopeptidases / Q000276:immunology / Q000378:metabolism*
D000936:Antigen-Antibody Complex; D018925:Chemokines; D016023:Integrins; D017382:Reactive Oxygen Species; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; C534096:Ctsg protein, mouse; D019272:Leukocyte Elastase