PMID- 17364026 OWN - NLM STAT- MEDLINE DCOM- 20070604 LR - 20220409 IS - 0021-9738 (Print) IS - 1558-8238 (Electronic) IS - 0021-9738 (Linking) VI - 117 IP - 4 DP - 2007 Apr TI - Critical roles for CCR2 and MCP-3 in monocyte mobilization from bone marrow and recruitment to inflammatory sites. PG - 902-9 AB - Monocyte recruitment to sites of inflammation is regulated by members of the chemokine family of chemotactic cytokines. However, the mechanisms that govern the migration of monocytes from bone marrow to blood and from blood to inflamed tissues are not well understood. Here we report that CC chemokine receptor 2 (CCR2) is highly expressed on a subpopulation of blood monocytes whose numbers are markedly decreased in CCR2(-/-) mice. In bone marrow, however, CCR2(-/-) mice had an increased number of monocytes, suggesting that CCR2 is critical for monocyte egress. Intravenous infusion of ex vivo-labeled WT or CCR2(-/-) bone marrow into WT recipient mice demonstrated that CCR2 is necessary for efficient monocyte recruitment from the blood to inflamed tissue. Analysis of mice lacking monocyte chemoattractant protein-1 (MCP-1), MCP-3, MCP-5, or MCP-2 plus MCP-5 revealed that MCP-3 and MCP-1 are the CCR2 agonists most critical for the maintenance of normal blood monocyte counts. These findings provide evidence that CCR2 and MCP-3/MCP-1 are critical for monocyte mobilization and suggest new roles for monocyte chemoattractants in leukocyte homeostasis. FAU - Tsou, Chia-Lin AU - Tsou CL AD - Gladstone Institute of Cardiovascular Disease, UCSF, San Francisco, California 94158, USA. FAU - Peters, Wendy AU - Peters W FAU - Si, Yue AU - Si Y FAU - Slaymaker, Sarah AU - Slaymaker S FAU - Aslanian, Ara M AU - Aslanian AM FAU - Weisberg, Stuart P AU - Weisberg SP FAU - Mack, Matthias AU - Mack M FAU - Charo, Israel F AU - Charo IF LA - eng GR - R01 HL052773/HL/NHLBI NIH HHS/United States GR - R01 HL063894/HL/NHLBI NIH HHS/United States GR - 5R01 HL52773-12/HL/NHLBI NIH HHS/United States GR - R01 HL63894-07/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20070315 PL - United States TA - J Clin Invest JT - The Journal of clinical investigation JID - 7802877 RN - 0 (CCL7 protein, human) RN - 0 (CCR2 protein, human) RN - 0 (Ccl7 protein, mouse) RN - 0 (Ccr2 protein, mouse) RN - 0 (Chemokine CCL7) RN - 0 (Chemokines) RN - 0 (Monocyte Chemoattractant Proteins) RN - 0 (Receptors, CCR2) RN - 0 (Receptors, Chemokine) SB - IM MH - Adoptive Transfer MH - Animals MH - Blood Cell Count MH - Bone Marrow Cells/*physiology MH - Bone Marrow Transplantation/physiology MH - Chemokine CCL7 MH - Chemokines/blood MH - Humans MH - Inflammation/*physiopathology MH - Mice MH - Mice, Knockout MH - Monocyte Chemoattractant Proteins/genetics/*physiology MH - Monocytes/immunology/*physiology MH - Polymorphism, Genetic MH - Receptors, CCR2 MH - Receptors, Chemokine/deficiency/genetics/*physiology PMC - PMC1810572 EDAT- 2007/03/17 09:00 MHDA- 2007/06/05 09:00 PMCR- 2007/04/02 CRDT- 2007/03/17 09:00 PHST- 2006/07/31 00:00 [received] PHST- 2007/01/24 00:00 [accepted] PHST- 2007/03/17 09:00 [pubmed] PHST- 2007/06/05 09:00 [medline] PHST- 2007/03/17 09:00 [entrez] PHST- 2007/04/02 00:00 [pmc-release] AID - 29919 [pii] AID - 10.1172/JCI29919 [doi] PST - ppublish SO - J Clin Invest. 2007 Apr;117(4):902-9. doi: 10.1172/JCI29919. Epub 2007 Mar 15.