The Journal of Experimental Medicine
Torrey Pines Biolabs
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article
Right arrow Full Text
Right arrow Full Text (PDF, 137K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lu, B.
Right arrow Articles by Rollins, B. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lu, B.
Right arrow Articles by Rollins, B. J.
Social Bookmarking
 Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
© The Rockefeller University Press, 0022-1007/1998/2/601/ $5.00
The Journal of Experimental Medicine, Volume 187, Number 4, February 16, 1998 601-608


Articles

Abnormalities in Monocyte Recruitment and Cytokine Expression in Monocyte Chemoattractant Protein 1–deficient Mice

Bao Lu{ddagger}, Barbara J. Rutledge*, Long Gu*, Joseph Fiorillo*, Nicholas W. Lukacs§, Steven L. Kunkel§, Robert North, Craig Gerard{ddagger}, and Barrett J. Rollins*

From the * Department of Adult Oncology, Dana-Farber Cancer Institute, and the {ddagger} 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 {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.


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: 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.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS