Leptin is an eosinophil survival factor
Leptin is an eosinophil survival factor
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DOI：
10.1016/j.jaci.2005.09.003
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发表时间：
2005-12-01
影响因子：
14.2
通讯作者：
Simon, HU
中科院分区：
文献类型：
--
作者：
Conus, S;Bruno, A;Simon, HU
背景：瘦素调节食物摄入，以及代谢、内分泌和免疫功能。它在包括T细胞在内的多种细胞类型中发挥增殖和抗凋亡活性。瘦素也刺激巨噬细胞和中性粒细胞，在炎症期间它的产生增加。目的：探讨瘦素受体在嗜酸性粒细胞中的表达及重组瘦素对细胞凋亡通路的影响。方法：采用RT-PCR和免疫荧光法检测新鲜分离的血嗜酸性粒细胞和组织嗜酸性粒细胞中瘦素受体的存在。利用流式细胞术、免疫印迹和免疫荧光技术研究了重组瘦素对嗜酸性粒细胞凋亡通路的影响。结果：人嗜酸性粒细胞在体外和体内均表达瘦素表面受体，瘦素延缓成熟嗜酸性粒细胞体外凋亡。瘦素的抗凋亡作用具有浓度依赖性，可被抗瘦素受体单克隆抗体阻断。瘦素对嗜酸性粒细胞凋亡的抑制作用与GM-CSF相似。瘦素延缓了Bax的切割，以及线粒体细胞色素c和第二线粒体来源的半胱天冬酶激活剂的释放，这表明它阻断了嗜酸性粒细胞线粒体附近的促凋亡途径。使用药物抑制剂，我们获得了瘦素在嗜酸性粒细胞中启动涉及磷脂酰肌醇-3- oh激酶和丝裂原活化蛋白激酶依赖途径的信号级联的证据。结论：瘦素是人类嗜酸性粒细胞的生存细胞因子，在变应性疾病和寄生虫病中具有潜在的病理相关性。
Background: Leptin regulates food intake, as well as metabolic, endocrine, and immune functions. It exerts proliferative and antiapoptotic activities in a variety of cell types, including T cells. Leptin also stimulates macrophages and neutrophils, and its production is increased during inflammation.Objective: We sought to examine the expression of leptin receptors on eosinophils and the effect of recombinant leptin on proapoptotic pathways in these cells.Methods: The presence of leptin receptor was examined by means of RT-PCR and immunofluorescence analysis in freshly isolated blood eosinophils and tissue eosinophils. The effect of recombinant leptin on apoptotic pathways in eosinophils was studied by using flow cytometric, immunoblotting, and immunofluorescence techniques.Results: Human eosinophils express leptin surface receptors under in vitro and in vivo conditions, and leptin delays apoptosis of mature eosinophils in vitro. The antiapoptotic effects of leptin were concentration dependent and blocked by an anti-leptin receptor mAb. The efficacy of leptin to block eosinophil apoptosis was similar to that of GM-CSF. Leptin delayed the cleavage of Bax, as well as the mitochondrial release of cytochrome c and second mitochondria-derived activator of caspase, suggesting that it blocks proapoptotic pathways proximal to mitochondria in eosinophils. Using pharmacological inhibitors, we obtained evidence that leptin initiates a signaling cascade involving phosphatidylinositol-3-OH kinase and mitogen-activated protein kinase-dependent pathways in eosinophils.Conclusion: Leptin is a survival cytokine for human eosinophils, a finding with potential pathologic relevance in allergic and parasitic diseases.