Leptin Enhances Survival and Induces Migration, Degranulation, and Cytokine Synthesis of Human Basophils
Leptin Enhances Survival and Induces Migration, Degranulation, and Cytokine Synthesis of Human Basophils
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DOI：
10.4049/jimmunol.1004054
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发表时间：
2011-05-01
影响因子：
4.4
通讯作者：
Ohta, Ken
中科院分区：
文献类型：
--
作者：
Suzukawa, Maho;Nagase, Hiroyuki;Ohta, Ken
嗜碱性粒细胞是人类血液中最稀有的白细胞，但现在被认为是变应性炎症中最重要的免疫调节细胞和效应细胞之一。瘦素是IL-6细胞因子家族的一员，作为一种脂肪因子具有代谢作用，并参与炎症反应的发病机制。由于肥胖和过敏之间存在流行病学关系，我们研究了瘦素是否会改变嗜碱性粒细胞的功能。我们发现，人嗜碱性粒细胞在mRNA和表面蛋白水平都表达瘦素受体(Lepr)，IL-33上调了Lepr的表达。瘦素对多种嗜碱性细胞功能有很强的影响。它在人嗜碱性粒细胞中诱导了强烈的迁移反应，其效力类似于嗜碱性粒细胞活性趋化因子。此外，瘦素提高了人类嗜碱性粒细胞的存活率，尽管其效力低于IL-3。此外，细胞表面表达的嗜碱性粒细胞活化标志CD63被瘦素上调，这种作用可被Lepr阻断而中和。对嗜碱性粒细胞脱颗粒和细胞因子合成的评估发现，瘦素对Fc epsilon RI聚集的人嗜碱性粒细胞脱颗粒有很强的启动作用，并诱导细胞产生Th2，但不诱导Th1细胞因子的产生。综上所述，目前的研究结果表明，瘦素可能是一个关键分子，通过与Lepr结合并激活细胞功能，介导脂肪细胞对嗜碱性粒细胞等炎性细胞的影响，从而可能加剧过敏性炎症。免疫学杂志，2011,186：5254-5260。
Basophils are the rarest leukocytes in human blood, but they are now recognized as one of the most important immunomodulatory as well as effector cells in allergic inflammation. Leptin, a member of the IL-6 cytokine family, has metabolic effects as an adipokine, and it is also known to participate in the pathogenesis of inflammatory reactions. Because there is an epidemiologic relationship between obesity and allergy, we examined whether basophil functions are modified by leptin. We found that human basophils express leptin receptor (LepR) at both the mRNA and surface protein levels, which were upregulated by IL-33. Leptin exerted strong effects on multiple basophil functions. It induced a strong migratory response in human basophils, similar in potency to that of basophil-active chemokines. Also, leptin enhanced survival of human basophils, although its potency was less than that of IL-3. Additionally, CD63, a basophil activation marker expressed on the cell surface, was upregulated by leptin, an effect that was neutralized by blocking of LepR. Assessments of basophil degranulation and cytokine synthesis found that leptin showed a strong priming effect on human basophil degranulation in response to Fc epsilon RI aggregation and induced Th2, but not Th1, cytokine production by the cells. In summary, the present findings indicate that leptin may be a key molecule mediating the effects of adipocytes on inflammatory cells such as basophils by binding to LepR and activating the cellular functions, presumably exacerbating allergic inflammation. The Journal of Immunology, 2011, 186: 5254-5260.