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Perlmutter Laboratory, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115; the
Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48105; and the ¶ Trudeau Institute, Saranac Lake, New York 12983
Monocyte chemoattractant protein 1 (MCP-1) is a CC chemokine that attracts monocytes, memory T lymphocytes, and natural killer cells. Because other chemokines have similar target cell specificities and because CCR2, a cloned MCP-1 receptor, binds other ligands, it has been uncertain whether MCP-1 plays a unique role in recruiting mononuclear cells in vivo. To address this question, we disrupted SCYA2 (the gene encoding MCP-1) and tested MCP-1–deficient mice in models of inflammation. Despite normal numbers of circulating leukocytes and resident macrophages, MCP-1–/– mice were specifically unable to recruit monocytes 72 h after intraperitoneal thioglycollate administration. Similarly, accumulation of F4/80+ monocytes in delayed-type hypersensitivity lesions was impaired, although the swelling response was normal. Development of secondary pulmonary granulomata in response to Schistosoma mansoni eggs was blunted in MCP-1–/– mice, as was expression of IL-4, IL-5, and interferon
in splenocytes. In contrast, MCP-1–/– mice were indistinguishable from wild-type mice in their ability to clear Mycobacterium tuberculosis. Our data indicate that MCP-1 is uniquely essential for monocyte recruitment in several inflammatory models in vivo and influences expression of cytokines related to T helper responses.
This work was funded by National Institutes of Health grants CA-53091, HL-35276, and HL-51366. B.J. Rollins is a Scholar of the Leukemia Society of America.
Address correspondence to Barrett Rollins, Dana-Farber Cancer Institute, 44 Binney St., Boston, MA 02115. Phone: 617-632-3896; Fax: 617-632-5417; E-mail: barrett_rollins{at}dfci.harvard.edu
1 Abbreviations used in this paper: DNFB, 2,4-dinitro-1-fluorobenzene; DTH, delayed-type hypersensitivity; MCP, monocyte chemoattractant protein; MIP, macrophage inflammatory protein; SEA, Schistosome egg antigen.
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