Role of CC chemokine receptor 2 in bone marrow cells in the recruitment of macrophages into obese adipose tissue.
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.
Ito
Ayaka
A
Department of Molecular Medicine and Metabolism, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Tokyo 113-8510, Japan.
Suganami
Takayoshi
T
Yamauchi
Akira
A
Degawa-Yamauchi
Mikako
M
Tanaka
Miyako
M
Kouyama
Ryuji
R
Kobayashi
Yuko
Y
Nitta
Nao
N
Yasuda
Kazuki
K
Hirata
Yukio
Y
Kuziel
William A
WA
Takeya
Motohiro
M
Kanegasaki
Shiro
S
Kamei
Yasutomi
Y
Ogawa
Yoshihiro
Y
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
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