TY - JOUR
T1 - Serine protease cathepsin G regulates adhesion-dependent neutrophil effector functions by modulating integrin clustering
AU - Raptis, Sofia Z.
AU - Shapiro, Steven D.
AU - Simmons, Pamela M.
AU - Cheng, Alec M.
AU - Pham, Christine T.N.
N1 - Funding Information:
The authors thank Ying Hu for excellent technical assistance, and Hector Molina (Washington University) and Sherman Fong (Genentech, Inc.) for helpful discussions and critically reading the manuscript. We thank Kathy Liszewski and Wojciech Swat for expert technical advice and reagents. We thank Tim Ley and Wayne Yokoyama for their continued support. This work was partially supported by a Biomedical Science Award from the Arthritis Foundation (C.T.N.P) and National Institutes of Health grants AI49261, P30AR48335 (C.T.N.P.), and HL54853 (S.D.S).
PY - 2005/6
Y1 - 2005/6
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/20444433960
U2 - 10.1016/j.immuni.2005.03.015
DO - 10.1016/j.immuni.2005.03.015
M3 - Article
C2 - 15963783
AN - SCOPUS:20444433960
SN - 1074-7613
VL - 22
SP - 679
EP - 691
JO - Immunity
JF - Immunity
IS - 6
ER -