Unité de Pharmacologie Cellulaire, Unité Associée IP/INSERM 485, Institut Pasteur, Paris, France
Correspondence: Dr. Michel Chignard, Unité de Pharmacologie Cellulaire, Unité Associée IP/INSERM 485, Institut Pasteur, 25, rue du Docteur Roux, F-75724 Paris Cédex 15, France. E-mail: chignard{at}pasteur.fr
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 
(TNF-) 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 (Mr = 57,000) is directly cleaved by CG and released into the extracellular
medium as a high-Mr species
(Mr = 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.
Key Words: serine proteinase • TNF- • inflammation
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