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PMID: 9463410 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The Journal of experimental medicine ·Vol. 187 ·No. 4 ·1998-02-16 ·Pages 601-8

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

Abstract

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.

MeSH Terms
Animals Antigens, Helminth/immunology Chemokine CCL2/deficiency,genetics,physiology Cytokines/biosynthesis Dermatitis, Contact/immunology Disease Models, Animal Female Gene Targeting Granuloma, Respiratory Tract/immunology,parasitology Hypersensitivity, Delayed/immunology Inflammation/immunology Interferon-gamma/biosynthesis Interleukin-4/biosynthesis Interleukin-5/biosynthesis Male Mice Monocytes/immunology,physiology Mycobacterium bovis/immunology Phenotype Schistosomiasis mansoni/immunology Tuberculosis/immunology
Chemicals
Antigens, Helminth Chemokine CCL2 Cytokines Interleukin-5 Interleukin-4 Interferon-gamma
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Lu B
Perlmutter Laboratory, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Rutledge B J
Gu L
Fiorillo J
Lukacs N W
Kunkel S L
North R
Gerard C
Rollins B J
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.187.4.601
Published
1998-02-16
Pages
601-8
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2212142
Subset
IM
Grants
NHLBI NIH HHS · HL-51366 · United States
NHLBI NIH HHS · HL-35276 · United States
NCI NIH HHS · CA-53091 · United States
External Links
PubMed source DOI: 10.1084/jem.187.4.601 PMC Full Text View journal details
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