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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.

This work was supported by National Institutes of Health grants to A.D. Luster (CA69212), I.F. Charo (HL52773), and J. MacLean (AI01245), a Cancer Research Institute/Benjamin Jacobson Family Investigator Award to A.D. Luster and a Fogarty International Fellowship to E.A. Garcia-Zepeda.

¹Abbreviations used in this paper: CCR, CC chemokine receptor; MCP, monocyte chemoattractant protein; MIP, macrophage inflammatory protein; Nb, Nippostronglyus brasiliensis; RACE, rapid amplification of cDNA ends; rp, ribosomal protein; SSCP, single-strand conformation polymorphism; SVEC, SV-40 immortalized murine endothelial cell line.

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