Apoptotic pathways are inhibited by leptin receptor activation in neutrophils
Apoptotic pathways are inhibited by leptin receptor activation in neutrophils
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DOI：
10.4049/jimmunol.174.12.8090
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发表时间：
2005-06-15
影响因子：
4.4
通讯作者：
Simon, HU
中科院分区：
文献类型：
--
作者：
Bruno, A;Conus, S;Simon, HU
瘦素调节食物摄入量以及代谢、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。瘦素还可以刺激巨噬细胞和中性粒细胞，在炎症期间其产量会增加。在这项研究中，我们证明了在体外和体内条件下，人中性粒细胞表达瘦素表面受体，并且瘦素在体外延缓了成熟中性粒细胞的凋亡。瘦素的抗细胞凋亡作用呈浓度依赖性，并可被抗瘦素受体单抗阻断。瘦素阻断中性粒细胞凋亡的作用与G-CSF相似。利用药物抑制剂，我们获得了证据表明，瘦素在中性粒细胞中启动了涉及PI3K和MAPK依赖通路的信号级联反应。此外，Leptin还延迟了Bid和Bax的裂解，细胞色素c和caspase第二激活物的线粒体释放，以及caspase-8和caspase-3的激活。综上所述，瘦素是人类中性粒细胞的存活细胞因子，这一发现与炎症性疾病的潜在病理相关。
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. In this study, we demonstrate that human neutrophils express leptin surface receptors under in vitro and in vivo conditions, and that leptin delays apoptosis of mature neutrophils in vitro. The antiapoptotic effects of leptin were concentration dependent and blocked by an anti-leptin receptor mAb. The efficacy of leptin to block neutrophil apoptosis was similar to G-CSF. Using pharmacological inhibitors, we obtained evidence that leptin initiates a signaling cascade involving PI3K- and MAPK-dependent pathways in neutrophils. Moreover, leptin delayed the cleavage of Bid and Bax, the mitochondrial release of cytochrome c and second mitochondria-derived activator of caspase, as well as the activation of both caspase-8 and caspase-3 in these cells. Taken together, leptin is a survival cytokine for human neutrophils, a finding with potential pathologic relevance in inflammatory diseases.