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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16 February 1998
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February 16 1998
Abnormalities in Monocyte Recruitment and Cytokine Expression in Monocyte Chemoattractant Protein 1–deficient Mice
Bao Lu,
Bao Lu
From the *Department of Adult Oncology, Dana-Farber Cancer Institute, and the ‡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
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Barbara J. Rutledge,
Barbara J. Rutledge
From the *Department of Adult Oncology, Dana-Farber Cancer Institute, and the ‡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
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Long Gu,
Long Gu
From the *Department of Adult Oncology, Dana-Farber Cancer Institute, and the ‡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
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Joseph Fiorillo,
Joseph Fiorillo
From the *Department of Adult Oncology, Dana-Farber Cancer Institute, and the ‡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
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Nicholas W. Lukacs,
Nicholas W. Lukacs
From the *Department of Adult Oncology, Dana-Farber Cancer Institute, and the ‡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
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Steven L. Kunkel,
Steven L. Kunkel
From the *Department of Adult Oncology, Dana-Farber Cancer Institute, and the ‡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
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Robert North,
Robert North
From the *Department of Adult Oncology, Dana-Farber Cancer Institute, and the ‡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
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Craig Gerard,
Craig Gerard
From the *Department of Adult Oncology, Dana-Farber Cancer Institute, and the ‡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
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Barrett J. Rollins
Barrett J. Rollins
From the *Department of Adult Oncology, Dana-Farber Cancer Institute, and the ‡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
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Bao Lu
From the *Department of Adult Oncology, Dana-Farber Cancer Institute, and the ‡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
Barbara J. Rutledge
From the *Department of Adult Oncology, Dana-Farber Cancer Institute, and the ‡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
Long Gu
From the *Department of Adult Oncology, Dana-Farber Cancer Institute, and the ‡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
Joseph Fiorillo
From the *Department of Adult Oncology, Dana-Farber Cancer Institute, and the ‡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
Nicholas W. Lukacs
From the *Department of Adult Oncology, Dana-Farber Cancer Institute, and the ‡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
Steven L. Kunkel
From the *Department of Adult Oncology, Dana-Farber Cancer Institute, and the ‡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
Robert North
From the *Department of Adult Oncology, Dana-Farber Cancer Institute, and the ‡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
Craig Gerard
From the *Department of Adult Oncology, Dana-Farber Cancer Institute, and the ‡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
Barrett J. Rollins
From the *Department of Adult Oncology, Dana-Farber Cancer Institute, and the ‡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
The authors thank Dr. Arlene Sharpe for blastocyst injections; Dr. Abul Abbas for helpful comments and encouragement; Drs. Rolf Freter and Charles Stiles for the 5′ genomic MCP-1 fragment; Dr. Maja Sirotkovic for technical help; and the staff of the Animal Resource Division at Dana-Farber Cancer Institute for its superb care and handling of the mice used in this study. We also appreciate the administrative support of Laurie Geronimo.
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: [email protected]
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.
Received:
October 14 1997
Revision Received:
December 02 1997
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1998
J Exp Med (1998) 187 (4): 601–608.
Article history
Received:
October 14 1997
Revision Received:
December 02 1997
Citation
Bao Lu, Barbara J. Rutledge, Long Gu, Joseph Fiorillo, Nicholas W. Lukacs, Steven L. Kunkel, Robert North, Craig Gerard, Barrett J. Rollins; Abnormalities in Monocyte Recruitment and Cytokine Expression in Monocyte Chemoattractant Protein 1–deficient Mice . J Exp Med 16 February 1998; 187 (4): 601–608. doi: https://doi.org/10.1084/jem.187.4.601
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