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

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 gamma 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.

Pubmed ID: 9463410

Authors

  • Lu B
  • Rutledge BJ
  • Gu L
  • Fiorillo J
  • Lukacs NW
  • Kunkel SL
  • North R
  • Gerard C
  • Rollins BJ

Journal

The Journal of experimental medicine

Publication Data

February 16, 1998

Associated Grants

  • Agency: NCI NIH HHS, Id: CA-53091
  • Agency: NHLBI NIH HHS, Id: HL-35276
  • Agency: NHLBI NIH HHS, Id: HL-51366

Mesh Terms

  • Animals
  • Antigens, Helminth
  • Chemokine CCL2
  • Cytokines
  • Dermatitis, Contact
  • Disease Models, Animal
  • Female
  • Gene Targeting
  • Granuloma, Respiratory Tract
  • Hypersensitivity, Delayed
  • Inflammation
  • Interferon-gamma
  • Interleukin-4
  • Interleukin-5
  • Male
  • Mice
  • Monocytes
  • Mycobacterium bovis
  • Phenotype
  • Schistosomiasis mansoni
  • Tuberculosis