Annexin 1 mediates the rapid anti-inflammatory effects of neutrophil-derived microparticles
Annexin 1 mediates the rapid anti-inflammatory effects of neutrophil-derived microparticles
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DOI：
10.1182/blood-2008-02-140533
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发表时间：
2008-09-15
期刊：
影响因子：
20.3
通讯作者：
Perretti, Mauro
中科院分区：
文献类型：
--
作者：
Dalli, Jesmond;Norling, Lucy V.;Perretti, Mauro
多形核白细胞(PMN)来源的微粒在体外显示出对靶细胞的抑制特性；由于PMN含有大量的内源性抗炎蛋白Annexin 1(AnxA1)，我们在这里测试了PMN来源的微粒中是否存在具有生物活性的AnxA1。通过Western blotting、流式细胞术和质谱分析检测，PMN与人脐静脉内皮细胞(HUVEC)单分子层的黏附导致了含有AnxA1的微粒的产生。在HUVEC单层上流动之前，将这些微粒添加到受体PMN中，可显著抑制细胞黏附，这种作用可被中和抗AnxA1抗体或抗AnxA1受体抗体消除，即脂氧素A(4)受体或ALX。静脉注射人PMN来源的微粒显著地抑制PMN向被IL-1β炎症的气囊中的募集。这种抗炎作用也依赖于内源性AnxA1，因为注射来自野生型PMN(骨髓来源的)的微粒，而不是来自AnxA1缺失的PMN的微粒，可以抑制IL-1β诱导的白细胞转移。总之，PMN来源的微粒含有功能活性的AnxA1，赋予它们抗炎特性；这些微粒在微循环中的产生可以通过依赖时间的抑制细胞募集来促进炎症的消退。
Polymorphonuclear leukocyte (PMN) derived microparticles display inhibitory properties on target cells as assessed in vitro; since PMNs contain abundant amounts of the endogenous anti-inflammatory protein annexin 1 (AnxA1), we tested here whether biologically active AnxA1 could be present in PMN-derived microparticles. PMN adhesion to human umbilical vein endothelial cell (HUVEC) monolayers led to the generation of microparticles that contained AnxA1, as detected by Western blotting, flow cytometry, and mass spectrometry analyses. Addition of these microparticles to recipient PMNs prior to flow over HUVEC monolayers significantly inhibited cell adhesion, an effect abrogated by a neutralizing anti-AnxA1 antibody, or an antibody raised against the AnxA1 receptor, that is termed lipoxin A(4) receptor or ALX. Intravenous delivery of human PMN-derived microparticles markedly inhibited PMN recruitment to an air pouch inflamed with IL-1 beta. This anti-inflammatory effect was also dependent on endogenous AnxA1, since injection of microparticles produced from wild-type PMNs (bone marrow derived), but not from AnxA1-null PMNs, inhibited IL-1 beta-induced leukocyte trafficking. In conclusion, PMN-derived microparticles contain functionally active AnxA1 that confers them anti-inflammatory properties; generation of these microparticles in the microcirculation could promote inflammatory resolution by time-dependent dampening of cell recruitment.