The platelet-activating factor signaling system and its regulators in syndromes of inflammation and thrombosis
The platelet-activating factor signaling system and its regulators in syndromes of inflammation and thrombosis
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DOI：
10.1097/00003246-200205001-00020
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发表时间：
2002-05-01
影响因子：
8.8
通讯作者：
Stafforini, DM
中科院分区：
文献类型：
--
作者：
Zimmerman, GA;McIntyre, TM;Stafforini, DM
目的：回顾血小板活化因子（PAF）信号系统、其调节及其在急性炎症和血栓形成以及涉及这些级联反应的综合征（包括脓毒症）中的失调。数据来源：来自MEDLINE检索文件和已发表综述的已发表文献的总结。数据提取、合成和总结，PAF，一种磷脂信号分子，将由外向内的信号传递到各种细胞类型中的细胞内转导系统和效应器机制，包括先天免疫和止血系统的关键细胞：中性粒细胞、单核细胞和血小板。因此，PAF信号传导系统是一个汇聚点，在该汇聚点处，有害刺激可以触发和放大急性炎症级联反应和血栓级联反应。PAF的生物学活性受到多种精确机制的调节，这些机制共同限制和控制其在生理炎症中的作用。PAF的合成失调或限制其生物活性的机制缺陷有可能导致病理性炎症和血栓形成。此外，被PAF受体识别的氧化磷脂的非酶促生成可触发炎症和血栓形成事件。有证据表明PAF信号系统在脓毒症、休克和创伤性损伤中失调，并且其效应器反应的中断或终止导致有益的结果。血浆PAF乙酰水解酶，一种酶，水解PAF和结构相关的氧化磷脂，产生的产品，不再被PAF receptor recognized，可能是一个特别重要的信号terminator.Conclusion：PAF信号系统可以触发炎症和血栓级联反应，放大这些级联反应时，与其他介质，并介导炎症和血栓形成之间的分子和细胞的相互作用（串扰）。来自体外实验、实验动物研究和人类临床观察的证据表明，PAF信号传导系统在脓毒症和其他炎性损伤综合征中是重要的，并且阻断或终止经由PAF信号传导系统的信号传导的治疗策略在这些病症中可能是有用的。
Objectives: To review the platelet-activating factor (PAF) signaling system, its regulation, and its dysregulation in acute inflammation and thrombosis and In syndromes that involve these cascades, including sepsis.Data Sources: A summary of published literature from MEDLINE search files and published reviews.Data Extraction, Synthesis, and Summary, PAF, a phospholipid signaling molecule, transmits outside-in signals to intracellular transduction systems and effector mechanisms in a variety of cell types, including key cells of the Innate immune and hemostatic systems: neutrophils, monocytes, and platelets. Thus, the PAF signaling system Is a point of convergence at which injurious stimuli can trigger and amplify both acute inflammatory and thrombotic cascades. The biological activities of PAF are regulated by several precise mechanisms that, together, constrain and control its action in physiologic Inflammation. Unregulated synthesis of PAF or defects in the mechanisms that limit its biological activities have the potential to cause pathologic Inflammation and thrombosis. In addition, nonenzymatic generation of oxidized phospholipids that are recognized by the PAF receptor can trigger inflammatory and thrombotic events. There is evidence that the PAF signaling system is dysregulated in sepsis, shock, and traumatic injury and that interruption or termination of its effector responses leads to beneficial outcomes. Plasma PAF acetylhydrolase, an enzyme that hydrolyzes PAF and structurally related oxidized phospholipids, yielding products that are no longer recognized by the PAF receptor, may be a particularly important signal terminator.Conclusion: The PAF signaling system can trigger inflammatory and thrombotic cascades, amplify these cascades when acting with other mediators, and mediate molecular and cellular interactions (cross talk) between inflammation and thrombosis. Evidence from in vitro experiments, studies of experimental animals, and clinical observations in humans indicates that the PAF signaling system is important in sepsis and other syndromes of inflammatory injury and that therapeutic strategies to Interrupt or terminate signaling via the PAF signaling system may be useful In these conditions.