β3-Adrenergic Receptor Stimulation Induces E-Selectin-mediated Adipose Tissue Inflammation
β3-Adrenergic Receptor Stimulation Induces E-Selectin-mediated Adipose Tissue Inflammation
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DOI：
10.1074/jbc.m112.412346
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发表时间：
2013-01-25
影响因子：
4.8
通讯作者：
Czech, Michael P.
中科院分区：
文献类型：
--
作者：
Flach, Rachel J. Roth;Matevossian, Anouch;Czech, Michael P.
伤口愈合或感染引起的炎症激活局部血管内皮细胞，通过上调白细胞粘附分子（如E-选择素和P-选择素）介导白细胞滚动、粘附和外渗。肥胖相关的脂肪组织炎症被认为会导致胰岛素抵抗，但体重减轻和脂肪分解也会促进脂肪组织免疫反应。虽然肥胖诱导的脂肪组织炎症需要白细胞-内皮相互作用，但尚不清楚脂肪分解诱导的炎症是否需要内皮细胞的激活。在这里，我们发现 CL 316,243 刺激 β(3)-肾上腺素能受体可促进野生型和 P-选择素缺失小鼠的脂肪组织中性粒细胞浸润，但不会促进 E-选择素缺失小鼠的脂肪组织中性粒细胞浸润。响应 CL 316,243 给药，脂肪组织细胞因子 IL-1β、CCL2 和 TNF-α 表达增加也依赖于 E-选择素，但不依赖于 P-选择素。相比之下，禁食会增加脂肪驻留的巨噬细胞，但不会增加中性粒细胞，并且不会激活脂肪驻留的内皮细胞。因此，脂解诱导的炎症的两种模型在脂肪组织内诱导不同的免疫细胞群，并表现出对内皮激活的不同依赖性。重要的是，我们的结果表明β(3)-肾上腺素能刺激通过上调脂肪组织内皮细胞中的E-选择素来诱导中性粒细胞浸润。
Inflammation induced by wound healing or infection activates local vascular endothelial cells to mediate leukocyte rolling, adhesion, and extravasation by up-regulation of leukocyte adhesion molecules such as E-selectin and P-selectin. Obesity-associated adipose tissue inflammation has been suggested to cause insulin resistance, but weight loss and lipolysis also promote adipose tissue immune responses. While leukocyte-endothelial interactions are required for obesity-induced inflammation of adipose tissue, it is not known whether lipolysis-induced inflammation requires activation of endothelial cells. Here, we show that beta(3)-adrenergic receptor stimulation by CL 316,243 promotes adipose tissue neutrophil infiltration in wild type and P-selectin-null mice but not in E-selectin-null mice. Increased expression of adipose tissue cytokines IL-1 beta, CCL2, and TNF-alpha in response to CL 316,243 administration is also dependent upon E-selectin but not P-selectin. In contrast, fasting increases adipose-resident macrophages but not neutrophils, and does not activate adipose-resident endothelium. Thus, two models of lipolysis-induced inflammation induce distinct immune cell populations within adipose tissue and exhibit distinct dependences on endothelial activation. Importantly, our results indicate that beta(3)-adrenergic stimulation acts through up-regulation of E-selectin in adipose tissue endothelial cells to induce neutrophil infiltration.