Critical roles for CCR2 and MCP-3 in monocyte mobilization from bone marrow and recruitment to inflammatory sites.
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.
Tsou
Chia-Lin
CL
Gladstone Institute of Cardiovascular Disease, UCSF, San Francisco, California 94158, USA.
Peters
Wendy
W
Si
Yue
Y
Slaymaker
Sarah
S
Aslanian
Ara M
AM
Weisberg
Stuart P
SP
Mack
Matthias
M
Charo
Israel F
IF
D019264:Adoptive Transfer; D000818:Animals; D001772:Blood Cell Count; D001854:Bone Marrow Cells / Q000502:physiology*; D016026:Bone Marrow Transplantation / Q000502:physiology; D054410:Chemokine CCL7; D018925:Chemokines / Q000097:blood; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D018945:Monocyte Chemoattractant Proteins / Q000235:genetics / Q000502:physiology*; D009000:Monocytes / Q000276:immunology / Q000502:physiology*; D011110:Polymorphism, Genetic; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
C515450:CCL7 protein, human; C515334:CCR2 protein, human; C515451:Ccl7 protein, mouse; C515335:Ccr2 protein, mouse; D054410:Chemokine CCL7; D018925:Chemokines; D018945:Monocyte Chemoattractant Proteins; D054390:Receptors, CCR2; D019707:Receptors, Chemokine