High level monocyte chemoattractant protein-1 expression in transgenic mice increases their susceptibility to intracellular pathogens

B. J. Rutledge, H. Rayburn, R. Rosenberg, R. J. North, R. P. Gladue, Christopher Corless, B. J. Rollins

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Abstract

We have constructed transgenic mice in which the mouse mammary tumor virus long terminal repent controls the expression of murine monocyte chemoattractant protein-1 (MCP-1). Several independently derived lines of transgenic mice constitutively expressed MCP-1 protein in a variety of organs. Protein extracts from these organs had substantial in vitro monocyte chemoattractant activity that was neutralized by an anti-MCP-1 Ab, indicating that transgenic MCP-1 protein is biologically active. However, no transgenic mouse at any age displayed monocyte infiltrates in MCP-1-expressing organs. Two transgenic lines had circulating MCP-1 levels of 13 to 26 ng/ml, which is a concentration sufficient to induce maximal monocyte chemotaxis in vitro. These transgenic lines showed a 1 to 1.5 log greater sensitivity to infection with Listeria monocytogenes and Mycobacterium tuberculosis. A third transgenic line had lower serum levels of MCP-1 and was resistant to L. monocytogenes. The results suggest that this transgenic model is one of monocyte nonresponsiveness to locally produced MCP-1 due to either receptor desensitization or neutralization of a chemoattractant gradient by high systemic concentrations of MCP-1. Regardless of the mechanism, the data indicate that constitutively high levels of MCP-1 expression do not induce monocytic infiltrates, and that MCP-1 is involved in the host response to intracellular pathogens.

Original languageEnglish (US)
Pages (from-to)4838-4843
Number of pages6
JournalJournal of Immunology
Volume155
Issue number10
Publication statusPublished - 1995
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology

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Rutledge, B. J., Rayburn, H., Rosenberg, R., North, R. J., Gladue, R. P., Corless, C., & Rollins, B. J. (1995). High level monocyte chemoattractant protein-1 expression in transgenic mice increases their susceptibility to intracellular pathogens. Journal of Immunology, 155(10), 4838-4843.