Monocyte chemoattractant protein-1 (MCP-1), not MCP-3, is the primary chemokine required for monocyte recruitment in thioglycollate-induced peritonitis (94.5)

Abstract

Abstract In this study, we generated a novel MCP-1-deficient (designated as MCP-1Ä/Ä) mouse model using the Cre/loxP system. As expected, MCP-1 was not produced by LPS-activated MCP-1Ä/Ä macrophages; however, the production of MCP-3 was unexpectedly increased. In contrast, macrophages from another mouse line with a neo gene cassette in intron 2 produced a significantly lower level of MCP-1 and MCP-3. Decreased MCP-3 production was also detected in previously generated MCP-1-deficient mice by the insertion of a neo gene cassette in exon 2 (designated as MCP-1 KO). Altered MCP-1 and/or MCP-3 production was observed in vivo in each mouse model in response to intraperitoneal injection of thioglycollate (TG). The up- and down-regulation of MCP-3 production in MCP-1Ä/Ä and MCP-1 KO mice, respectively, provided us with a unique opportunity to evaluate the role for MCP-3 in the recruitment of monocytes. Despite the increased MCP-3 production in MCP-1Ä/Ä mice, TG-induced monocyte accumulation was still reduced by about 50% compared to WT mice, which was similar to the reduction detected in MCP-1 KO mice. Thus, up-regulated MCP-3 production did not compensate for the loss of MCP-1, and MCP-3 appears to be a less effective mediator of monocyte recruitment than MCP-1 in this model. Our results also suggest the participation of other mediators regulating the recruitment of monocytes in this model.