Role of CC chemokine receptor 2 in bone marrow cells in the recruitment of macrophages into obese adipose tissue
Autor: | Yoshihiro Ogawa, Kazuki Yasuda, Ayaka Ito, Motohiro Takeya, Yuko Kobayashi, Yasutomi Kamei, Takayoshi Suganami, Shiro Kanegasaki, Miyako Tanaka, William A. Kuziel, Nao Nitta, Ryuji Kouyama, Mikako Degawa-Yamauchi, Yukio Hirata, Akira Yamauchi |
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Rok vydání: | 2008 |
Předmět: |
medicine.medical_specialty
CCR2 Receptors CCR2 animal diseases Adipose tissue macrophages Adipose tissue Antigens Differentiation Myelomonocytic Mice Obese Bone Marrow Cells Receptors Cell Surface Biology Biochemistry Proinflammatory cytokine Jurkat Cells Mice Antigens CD Cell Movement Internal medicine parasitic diseases medicine Animals Humans Lectins C-Type Obesity Molecular Biology Chemokine CCL2 Mice Knockout Monocyte Macrophages hemic and immune systems Cell Biology CD11c Antigen Toll-Like Receptor 4 medicine.anatomical_structure Endocrinology Mannose-Binding Lectins Adipose Tissue Bone marrow CC chemokine receptors Mannose receptor Mannose Receptor |
Zdroj: | The Journal of biological chemistry. 283(51) |
ISSN: | 0021-9258 |
Popis: | 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. |
Databáze: | OpenAIRE |
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