J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/03/969/06 $2.00
Volume 185, Number 5, March 3, 1997 969-974

BRIEF DEFINITIVE REPORT:
Bacterial Lipopolysaccharide Rapidly Inhibits Expression of C-C Chemokine Receptors in Human Monocytes

By Antonio Sica,^* Alessandra Saccani,^* Alessandro Borsatti,^* Christine A. Power, Timothy N.C. Wells, Walter Luini,^§ Nadia Polentarutti,^* Silvano Sozzani,^* and Alberto Mantovani^*§

From the ^* Istituto di Ricerche Farmacologiche "Mario Negri", 20157 Milan, Italy;  Laboratory of Molecular Biology, Istituto G. Gaslini, 16148 Genova-Quarto, Italy; ^§ Section of Pathology and Immunolgy, Department of Biotechnology, University of Brescia, 25123 Italy;  Geneva Biomedical Research Institute, Glaxo Wellcome Research and Development, 1228 Plan-les-Ouates, Geneva, Switzerland.

The present study was designed to investigate the effect of bacterial lipopolysaccharide (LPS) on C-C chemokine receptors (CCR) expressed in human mononuclear phagocytes. LPS caused a rapid and drastic reduction of CCR2 mRNA levels, which binds MCP-1 and -3. CCR1 and CCR5 mRNAs were also reduced, though to a lesser extent, whereas CXCR2 was unaffected. The rate of nuclear transcription of CCR2 was not affected by LPS, whereas the mRNA half life was reduced from 1.5 h to 45 min. As expected, LPS-induced inhibition of CCR2 mRNA expression was associated with a reduction of both MCP-1 binding and chemotactic responsiveness. The capacity to inhibit CCR2 expression in monocytes was shared by other microbial agents and cytokines (inactivated Streptococci, Propionibacterium acnes, and to a lesser extent, IL-1 and TNF-). In contrast, IL-2 augmented CCR2 expression and MCP-1 itself had no effect. These results suggest that, regulation of receptor expression in addition to agonist production is likely a crucial point in the regulation of the chemokine system.

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