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, C. L. Corless, B. J. Rollins

Research output: Contribution to journalArticle

168 Scopus citations

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
StatePublished - Jan 1 1995

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'High level monocyte chemoattractant protein-1 expression in transgenic mice increases their susceptibility to intracellular pathogens'. Together they form a unique fingerprint.

  • Cite this

    Rutledge, B. J., Rayburn, H., Rosenberg, R., North, R. J., Gladue, R. P., Corless, C. L., & 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.