PMID- 19641140 OWN - NLM STAT- MEDLINE DCOM- 20090918 LR - 20211028 IS - 1550-6606 (Electronic) IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 183 IP - 5 DP - 2009 Sep 1 TI - Monocyte chemoattractant protein-1 (MCP-1), not MCP-3, is the primary chemokine required for monocyte recruitment in mouse peritonitis induced with thioglycollate or zymosan A. PG - 3463-71 LID - 10.4049/jimmunol.0802812 [doi] AB - MCP-1/CCL2 plays a critical role in monocyte recruitment into sites of immune responses and cancer. However, the role of other MCPs remains unclear. In this study, we generated a novel MCP-1-deficient (designated as MCP-1(Delta/Delta)) mouse model by deleting a 2.3-kb DNA fragment from the mouse genome using the Cre/loxP system. MCP-1 was not produced by LPS-activated MCP-1(Delta/Delta) macrophages; however, the production of MCP-3, coded by the immediate downstream gene, was significantly 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 in which a neo-gene cassette was inserted in exon 2 (designated as MCP-1 knockout (KO)). Altered MCP-1 and/or MCP-3 production was also observed in vivo in each mouse model in response to i.p. injection of thioglycolate or zymosan. The up- and down-regulation of MCP-3 production in MCP-1(Delta/Delta) and MCP-1 KO mice, respectively, provided us with a unique opportunity to evaluate the role for MCP-3. Despite the increased MCP-3 production in MCP-1(Delta/Delta) mice, thioglycolate- or zymosan-induced monocyte/macrophage accumulation was still reduced by approximately 50% compared with wild-type mice, 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. Our results also indicate the presence of other mediators regulating the recruitment of monocytes in these models. FAU - Takahashi, Munehisa AU - Takahashi M AD - Laboratory of Molecular Immunoregulation, Cancer, and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. FAU - Galligan, Carole AU - Galligan C FAU - Tessarollo, Lino AU - Tessarollo L FAU - Yoshimura, Teizo AU - Yoshimura T LA - eng GR - Z01 BC010904/ImNIH/Intramural NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Intramural DEP - 20090729 PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Ccl2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Lipopolysaccharides) RN - 0 (Thioglycolates) RN - 9010-72-4 (Zymosan) RN - EC 3.4.17.1 (Carboxypeptidases A) RN - EC 3.4.17.1 (Cpa3 protein, mouse) SB - IM MH - Animals MH - Carboxypeptidases A/antagonists & inhibitors/biosynthesis/*physiology MH - Cell Movement/*immunology MH - Chemokine CCL2/deficiency/genetics/*physiology MH - Disease Models, Animal MH - Down-Regulation/genetics/immunology MH - Gene Deletion MH - Lipopolysaccharides/pharmacology MH - Macrophages, Peritoneal/immunology/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Monocytes/*cytology/*immunology/metabolism MH - Peritonitis/chemically induced/*immunology/pathology MH - Thioglycolates/administration & dosage/*pharmacology MH - Up-Regulation/immunology MH - Zymosan/administration & dosage/*pharmacology PMC - PMC7371094 MID - NIHMS1602095 COIS- Disclosures The authors have no financial conflict of interest. EDAT- 2009/07/31 09:00 MHDA- 2009/09/19 06:00 PMCR- 2020/07/20 CRDT- 2009/07/31 09:00 PHST- 2009/07/31 09:00 [entrez] PHST- 2009/07/31 09:00 [pubmed] PHST- 2009/09/19 06:00 [medline] PHST- 2020/07/20 00:00 [pmc-release] AID - jimmunol.0802812 [pii] AID - 10.4049/jimmunol.0802812 [doi] PST - ppublish SO - J Immunol. 2009 Sep 1;183(5):3463-71. doi: 10.4049/jimmunol.0802812. Epub 2009 Jul 29.