title: Role of CC chemokine receptor 2 in bone marrow cells in the recruitment of macrophages into obese adipose tissue.
abstract: The MCP-1 (monocyte chemoattractant protein-1)/CCR2 (CC motif chemokine receptor-2) pathway may play a role in macrophage infiltration into obese adipose tissue. Here we investigated the role of CCR2 in the recruitment of bone marrow-derived macrophages into obese adipose tissue in vitro and in vivo. Using the TAXIScan device, which can measure quantitatively the directionality and velocity of cell migration at time lapse intervals in vitro, we demonstrated that bone marrow cells (BMCs) from wild type mice migrate directly toward MCP-1 or culture medium conditioned by adipose tissue explants of genetically obese ob/ob mice, which are efficiently suppressed by pharmacological blockade of CCR2 signaling. The number of F4/80-positive macrophages was reduced in the adipose tissue from high fat diet-fed obese KKAy or ob/ob mice treated with a CCR2 antagonist propagermanium relative to vehicle-treated groups. We also found that the number of macrophages is reduced in the adipose tissue from ob/ob mice reconstituted with CCR2(-/-) BMCs (ob/ob + CCR2(-/-) BMCs) relative to those with CCR2+/+ BMCs (ob/ob + CCR2+/+ BMCs). Expression of mRNAs for CD11c and TLR4 (Toll-like receptor 4) markers of proinflammatory M1 macrophages was also decreased in the adipose tissue from ob/ob + CCR2(-/-) BMCs relative to ob/ob + CCR2+/+ BMCs, whereas mannose receptor and CD163, markers of anti-inflammatory M2 macrophages, were unchanged. This study provides in vivo and in vitro evidence that CCR2 in bone marrow cells plays an important role in the recruitment of macrophages into obese adipose tissue.
authors.affiliation: Department of Molecular Medicine and Metabolism, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Tokyo 113-8510, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Ito
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Suganami
authors.forename: Akira
authors.initials: A
authors.lastname: Yamauchi
authors.forename: Mikako
authors.initials: M
authors.lastname: Degawa-Yamauchi
authors.forename: Miyako
authors.initials: M
authors.lastname: Tanaka
authors.forename: Ryuji
authors.initials: R
authors.lastname: Kouyama
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Nao
authors.initials: N
authors.lastname: Nitta
authors.forename: Kazuki
authors.initials: K
authors.lastname: Yasuda
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hirata
authors.forename: William A
authors.initials: WA
authors.lastname: Kuziel
authors.forename: Motohiro
authors.initials: M
authors.lastname: Takeya
authors.forename: Shiro
authors.initials: S
authors.lastname: Kanegasaki
authors.forename: Yasutomi
authors.initials: Y
authors.lastname: Kamei
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ogawa
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology; D039521:CD11c Antigen / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008820:Mice, Obese; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D054390:Receptors, CCR2 / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C111835:CCL2 protein, human; C515334:CCR2 protein, human; D039521:CD11c Antigen; D000098902:CD163 Antigen; C491768:Ccl2 protein, mouse; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D054390:Receptors, CCR2; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4