TY - JOUR
T1 - High level monocyte chemoattractant protein-1 expression in transgenic mice increases their susceptibility to intracellular pathogens
AU - Rutledge, Barbara J.
AU - Rayburn, Helen
AU - Rosenberg, Robert
AU - North, Robert J.
AU - Gladue, Ronald P.
AU - Corless, Christopher L.
AU - Rollins, Barrett J.
PY - 1995
Y1 - 1995
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0028803841&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028803841&partnerID=8YFLogxK
M3 - Article
C2 - 7594486
AN - SCOPUS:0028803841
SN - 0022-1767
VL - 155
SP - 4838
EP - 4843
JO - Journal of Immunology
JF - Journal of Immunology
IS - 10
ER -