© The Rockefeller University Press, 0022-1007/1997/1/99/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 1, January 6, 1997 99-110
Murine Monocyte Chemoattractant Protein (MCP)-5: A Novel CC Chemokine That Is a Structural and Functional Homologue of Human MCP-1
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.
Address correspondence to Andrew D. Luster, Infectious Disease Unit, Massachusetts General Hospital-East, Building 149, 13th Street, Charlestown, MA 02129.
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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