Adiponectin binds to chemokines via the globular head and modulates interactions between chemokines and heparan sulfates
Adiponectin binds to chemokines via the globular head and modulates interactions between chemokines and heparan sulfates
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DOI：
10.1016/j.exphem.2007.03.010
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发表时间：
2007-06-01
影响因子：
2.6
通讯作者：
Kanakura, Yuzuru
中科院分区：
文献类型：
--
作者：
Masaie, Hiroaki;Oritani, Kenji;Kanakura, Yuzuru
目标。脂联素是一种脂肪细胞来源的蛋白质，由于其抗糖尿病和抗动脉粥样硬化的活性而引起人们的极大关注。本研究的目的是鉴定与脂联素生理相关的分子，并了解该蛋白如何表现出不同的生物学活性。采用表达克隆和酶联免疫吸附试验相结合的方法，从MS-5互补DNA文库中克隆脂联素结合蛋白。我们成功分离了基质细胞衍生因子-1(SDF-1)和CCF18两种趋化因子，并证实脂联素是通过其球形头部与其结合的。脂联素在体外与多种趋化因子结合，如巨噬细胞炎性蛋白-1α(MIP-1α)、RANTES和单核细胞趋化蛋白-1(MCP-1)，提示该蛋白具有与趋化因子家族结合的共同特征。趋化因子的中间部分被发现对脂联素的结合是重要的，它是与其受体相互作用所必需的。虽然脂联素与SDF-1的相互作用既不影响Jurkat细胞中SDF-1与CXCR4的结合，也不影响SDF-1的信号转导，但脂联素和肝素在体外相互干扰了它们与SDF-1和MCP-1的结合，提示它们的相互作用可能影响脂联素和SDF-1在炎症部位的分布。事实上，在急性移植物抗宿主病患者的肠道中，脂联素和SDF-1都呈阳性免疫染色。此外，脂联素基因缺陷小鼠外周血中造血祖细胞的数量高于野生型小鼠。脂联素可能通过与特定的趋化因子结合参与炎症的调节。此外，这种相互作用可能使脂联素在炎症部位聚集并发挥作用。(C)2007年国际实验血液学学会。由爱思唯尔公司出版。
Objective. Adiponectin, a fat cell-derived protein, has been attracting considerable attention because of its antidiabetic and antiatherogenic activities. The aim of the present study is to identify molecules physiologically associating with adiponectin and to understand how the protein displays diverse biological activities.Materials and Methods. We used an expression cloning method combined with enzyme-linked immunosorbent assay to clone adiponectin-binding proteins from the MS-5 complementary DNA library.Results. We successfully isolated two chemokines, stromal cell-derived factor-1 (SDF-1) and CCF18, and verified that adiponectin bound to them via its globular head. Adiponectin bound with various chemokines in vitro, such as macrophage-inflammatory protein-1 alpha (MIP-1 alpha), RANTES, and monocyte chemoattractant protein-1 (MCP-1), suggesting that the protein had a feature commonly to bind to the chemokine family. The middle part of chemokines, dispensable for interacting with their receptors, was found to be important for the adiponectin binding. Although the interaction of adiponectin to SDF-1 affected neither the SDF-1-CXCR4 binding nor the SDF-1 signaling in Jurkat cells, adiponectin and heparin mutually interfered in their association to SDF-1 and MCP-1 in vitro, implying that their association might influence the distribution of adiponectin and SDF-1 in inflammatory sites. Indeed, both adiponectin and SDF-1 was positively immunostained in vascular walls in guts from acute graft-vs-host disease patients. In addition, peripheral blood of adiponectin-deficient mice contained more hematopoietic progenitors than that of wild-type mice.Conclusion. Adiponectin may be involved in regulation of inflammation via binding to specific chemokines. Additionally, the interaction possibly enables adiponectin to gather and play its role in inflammatory sites. (c) 2007 International Society for Experimental Hematology. Published by Elsevier Inc.