Institute for Molecular Cardiovascular Research (IMCAR), RWTH University Aachen, Aachen, Germany.
Blood. 2009 Nov 19;114(21):4613-23. doi: 10.1182/blood-2009-06-221630. Epub 2009 Aug 20.
Extravasation of polymorphonuclear leukocytes (PMNs) to the site of inflammation precedes a second wave of emigrating monocytes. That these events are causally connected has been established a long time ago. However, we are now just beginning to understand the molecular mechanisms underlying this cellular switch, which has become even more complex considering the emergence of monocyte subsets, which are affected differently by signals generated from PMNs. PMN granule proteins induce adhesion as well as emigration of inflammatory monocytes to the site of inflammation involving beta(2)-integrins and formyl-peptide receptors. Furthermore, modification of the chemokine network by PMNs and their granule proteins creates a milieu favoring extravasation of inflammatory monocytes. Finally, emigrated PMNs rapidly undergo apoptosis, leading to the discharge of lysophosphatidylcholine, which attracts monocytes via G2A receptors. The net effect of these mechanisms is the accumulation of inflammatory monocytes, thus promoting proinflammatory events, such as release of inflammation-sustaining cytokines and reactive oxygen species. As targeting PMNs without causing serious side effects seems futile, it may be more promising to aim at interfering with subsequent PMN-driven proinflammatory events.
多形核白细胞 (PMN) 向炎症部位的渗出先于第二波迁移的单核细胞。很久以前就已经确定这些事件是因果相关的。然而，我们现在才刚刚开始了解这种细胞转换的分子机制，考虑到单核细胞亚群的出现，这种机制变得更加复杂，因为这些亚群受到 PMN 产生的信号的影响不同。PMN 颗粒蛋白诱导炎症单核细胞的粘附和迁移到炎症部位，涉及β(2)-整合素和甲酰肽受体。此外，PMN 及其颗粒蛋白对趋化因子网络的修饰为炎症单核细胞的渗出创造了有利环境。最后，迁移的 PMN 迅速发生凋亡，导致溶血磷脂酰胆碱的释放，通过 G2A 受体吸引单核细胞。这些机制的净效应是炎症性单核细胞的积累，从而促进促炎事件，如炎症维持细胞因子和活性氧的释放。由于靶向 PMN 而不引起严重副作用似乎没有希望，因此更有希望的是针对随后的 PMN 驱动的促炎事件进行干预。
