J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/01/99/12 $2.00
Volume 185 January 1997 99-110

Murine Monocyte Chemoattractant Protein (MCP)-5: A Novel CC Chemokine That Is a Structural and Functional Homologue of Human MCP-1

By Mindy N. Sarafi,^* Eduardo A. Garcia-Zepeda,^* James A. MacLean, Israel F. Charo,^§ and Andrew D. Luster^*

From the ^* Infectious Disease Unit,  Allergy and Immunology Unit, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts 02114; and the ^§ Gladstone Institute of Cardiovascular Disease; and Department of Medicine, University of California, San Francisco, California 94141

The chemokines are a large family of cytokines that control the recruitment of leukocytes in immune and inflammatory responses. We describe the isolation of a novel murine CC chemokine that, based on its biological and structural features, we have named monocyte chemoattractant protein (MCP)-5. MCP-5 mapped to the CC chemokine cluster on mouse chromosome 11 and was most closely related to human MCP-1 in structure (66% amino acid identity). Purified recombinant MCP-5 protein was a potent chemoattractant for peripheral blood monocytes, was only weakly active on eosinophils at high doses, and was inactive on neutrophils. MCP-5 induced a calcium flux in peripheral blood mononuclear cells, but not in purified murine eosinophils or neutrophils. Consistent with these results, MCP-5 induced a calcium flux in human embryonic kidney (HEK)-293 cells transfected with human and murine CCR2, a CC chemokine receptor expressed on monocytes. MCP-5 did not induce a calcium flux in HEK-293 cells transfected with CCR1, CCR3, or CCR5. Constitutive expression of MCP-5 mRNA was detected predominantly in lymph nodes, and its expression was markedly induced in macrophages activated in vitro and in vivo. Moreover, MCP-5 expression was upregulated in the lungs of mice following aerosolized antigen challenge of sensitized mice, and during the host response to infection with Nippostrongylus brasiliensis. These data indicate that MCP-5 is a novel and potent monocyte active chemokine that is involved in allergic inflammation and the host response to pathogens.

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