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Human neutrophil cathepsin G down‐regulates LPS‐mediated monocyte activation through CD14 proteolysis
Author(s) -
LeBarillec Karine,
Pidard Dominique,
Balloy Viviane,
Chignard Michel
Publication year - 2000
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.68.2.209
Subject(s) - cathepsin g , cd14 , biology , monocyte , proteinase 3 , lipopolysaccharide , tlr4 , cathepsin , extracellular , tumor necrosis factor alpha , microbiology and biotechnology , proteolysis , azurophilic granule , serine , flow cytometry , inflammation , myeloperoxidase , biochemistry , immunology , signal transduction , enzyme , phosphorylation
A major property of monocytes/macrophages is to recognize and to be activated by bacterial wall components such as LPS, through membrane receptors including the key element CD14. We demonstrate that CD14 expression is down‐regulated, as judged by flow cytometry analysis, upon incubation of human monocytes with purified cathepsin G (CG), a releasable neutrophil serine proteinase. The progressive decrease of CD14 expression due to increasing concentrations of CG highly correlates ( P < 0.0001) with the decreased synthesis of tumor necrosis factor α (TNF‐α) in response to lipopolysaccharide (LPS). This effect is dependent on the enzymatic activity of CG but is not exerted through an activation of monocytes. Immunoblot analysis reveals that CD14 ( M r = 57,000) is directly cleaved by CG and released into the extracellular medium as a high‐ M r species ( M r = 54,000). In this context, incubation of monocytes with activated neutrophils leads to a down‐regulation of CD14 expression, a process blocked by a serine proteinase inhibitor. These data suggest a paradoxical anti‐inflammatory property for CG.