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

Research output: Contribution to journalArticle

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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
StatePublished - 1995
Externally publishedYes

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Chemokine CCL2
Transgenic Mice
Monocytes
Chemotactic Factors
Listeria monocytogenes
Mouse mammary tumor virus
Proteins
Chemotaxis
Mycobacterium tuberculosis

ASJC Scopus subject areas

  • Immunology

Cite this

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.

High level monocyte chemoattractant protein-1 expression in transgenic mice increases their susceptibility to intracellular pathogens. / Rutledge, B. J.; Rayburn, H.; Rosenberg, R.; North, R. J.; Gladue, R. P.; Corless, Christopher; Rollins, B. J.

In: Journal of Immunology, Vol. 155, No. 10, 1995, p. 4838-4843.

Research output: Contribution to journalArticle

Rutledge, BJ, Rayburn, H, Rosenberg, R, North, RJ, Gladue, RP, Corless, C & Rollins, BJ 1995, 'High level monocyte chemoattractant protein-1 expression in transgenic mice increases their susceptibility to intracellular pathogens', Journal of Immunology, vol. 155, no. 10, pp. 4838-4843.
Rutledge, B. J. ; Rayburn, H. ; Rosenberg, R. ; North, R. J. ; Gladue, R. P. ; Corless, Christopher ; Rollins, B. J. / High level monocyte chemoattractant protein-1 expression in transgenic mice increases their susceptibility to intracellular pathogens. In: Journal of Immunology. 1995 ; Vol. 155, No. 10. pp. 4838-4843.
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