Serine protease cathepsin G regulates adhesion-dependent neutrophil effector functions by modulating integrin clustering

Immunity. 2005 Jun;22(6):679-91. doi: 10.1016/j.immuni.2005.03.015.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigen-Antibody Complex / immunology
  • Blotting, Western
  • Cathepsin G
  • Cathepsins / immunology
  • Cathepsins / metabolism*
  • Cell Adhesion / physiology*
  • Cells, Cultured
  • Chemokines / biosynthesis
  • Humans
  • Integrins / physiology*
  • Leukocyte Elastase / metabolism
  • Mice
  • Neutrophils / physiology*
  • Reactive Oxygen Species / metabolism
  • Respiratory Burst / physiology
  • Serine Endopeptidases / immunology
  • Serine Endopeptidases / metabolism*


  • Antigen-Antibody Complex
  • Chemokines
  • Integrins
  • Reactive Oxygen Species
  • Cathepsins
  • Serine Endopeptidases
  • CTSG protein, human
  • Cathepsin G
  • Ctsg protein, mouse
  • Leukocyte Elastase