A2A 腺苷受体对中性粒细胞产生的趋化因子谱的免疫调节作用。
Immunomodulatory impact of the A2A adenosine receptor on the profile of chemokines produced by neutrophils.
作者信息
McColl Shaun R, St-Onge Mireille, Dussault Andrée-Anne, Laflamme Cynthia, Bouchard Line, Boulanger Jean, Pouliot Marc
机构信息
Centre de Recherche en Rhumatologie et Immunologie du CHUQ (CHUL), and Department of Anatomy-Physiology, Faculty of Medicine, Laval University, Quebec, Canada.
出版信息
FASEB J. 2006 Jan;20(1):187-9. doi: 10.1096/fj.05-4804fje. Epub 2005 Nov 9.
In LPS-stimulated human neutrophils, engagement of the adenosine A2A receptor selectively prevented the expression and release of TNF-alpha, MIP-1alpha/CCL3, MIP-1beta/CCL4, MIP-2alpha/CXCL2, and MIP-3alpha/CCL20. In mice lacking the A2A receptor, granulocytes that migrated into the air pouch 4 h after LPS injection expressed higher mRNA levels of TNF-alpha, MIP-1alpha, and MIP-1beta than PMNs from wild-type mice. In mononuclear cells present in the air pouch 72 h after LPS injection, expression of IL-1beta, TNF-alpha, IL-6, and MCP-2/CCL6 was higher in A2AR knockout mice. In addition to highlighting neutrophils as an early and pivotal target for mediating adenosine anti-inflammatory activities, these results identify TNF-alpha and the MIP chemokine family as gene products whose expression is pivotally affected by activation of A2AR in LPS-activated PMNs. Modulation by A2AR in the production of inflammatory signals by PMNs may thus influence the evolution of an inflammatory response by reducing the activation status of inflammatory cells.
在脂多糖（LPS）刺激的人中性粒细胞中，腺苷A2A受体的激活选择性地抑制了肿瘤坏死因子-α（TNF-α）、巨噬细胞炎性蛋白-1α（MIP-1α/CCL3）、巨噬细胞炎性蛋白-1β（MIP-1β/CCL4）、巨噬细胞炎性蛋白-2α（MIP-2α/CXCL2）和巨噬细胞炎性蛋白-3α（MIP-3α/CCL20）的表达与释放。在缺乏A2A受体的小鼠中，LPS注射后4小时迁移至气腔的粒细胞中，TNF-α、MIP-1α和MIP-1β的mRNA水平高于野生型小鼠的多形核中性粒细胞（PMN）。在LPS注射后72小时气腔中的单核细胞中，A2A受体基因敲除小鼠中白细胞介素-1β（IL-1β）、TNF-α、IL-6和单核细胞趋化蛋白-2（MCP-2/CCL6）的表达更高。这些结果不仅突出了中性粒细胞作为介导腺苷抗炎活性的早期关键靶点，还确定了TNF-α和MIP趋化因子家族是LPS激活的PMN中A2A受体激活对其表达有关键影响的基因产物。因此，A2A受体对PMN产生炎症信号的调节可能通过降低炎症细胞的激活状态来影响炎症反应的发展。
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