Abnormalities in monocyte recruitment and cytokine expression in monocyte chemoattractant protein 1–deficient mice

B Lu, BJ Rutledge, L Gu, J Fiorillo, NW Lukacs… - The Journal of …, 1998 - rupress.org
B Lu, BJ Rutledge, L Gu, J Fiorillo, NW Lukacs, SL Kunkel, R North, C Gerard, BJ Rollins
The Journal of experimental medicine, 1998rupress.org
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 …
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 γ 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.
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