PMID- 7594486 OWN - NLM STAT- MEDLINE DCOM- 19951218 LR - 20101118 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 155 IP - 10 DP - 1995 Nov 15 TI - High level monocyte chemoattractant protein-1 expression in transgenic mice increases their susceptibility to intracellular pathogens. PG - 4838-43 AB - We have constructed transgenic mice in which the mouse mammary tumor virus long terminal repeat 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. FAU - Rutledge, B J AU - Rutledge BJ AD - Department of Medicine, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. FAU - Rayburn, H AU - Rayburn H FAU - Rosenberg, R AU - Rosenberg R FAU - North, R J AU - North RJ FAU - Gladue, R P AU - Gladue RP FAU - Corless, C L AU - Corless CL FAU - Rollins, B J AU - Rollins BJ LA - eng GR - CA53091/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Chemokine CCL2) SB - IM MH - Animals MH - Cell Movement MH - Chemokine CCL2/*biosynthesis/genetics/immunology MH - Chemotaxis MH - *Immune Tolerance MH - Listeria monocytogenes/*immunology/pathogenicity MH - Listeriosis/*immunology/pathology MH - Mice MH - Mice, Transgenic MH - Monocytes/*immunology MH - Mycobacterium tuberculosis/*immunology/pathogenicity MH - Tuberculosis/*immunology/pathology EDAT- 1995/11/15 00:00 MHDA- 1995/11/15 00:01 CRDT- 1995/11/15 00:00 PHST- 1995/11/15 00:00 [pubmed] PHST- 1995/11/15 00:01 [medline] PHST- 1995/11/15 00:00 [entrez] PST - ppublish SO - J Immunol. 1995 Nov 15;155(10):4838-43.