The Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada.
Am J Physiol Lung Cell Mol Physiol. 2012 Sep;303(5):L364-81. doi: 10.1152/ajplung.00354.2011. Epub 2012 Jun 22.
The pathophysiology of acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), is characterized by increased vascular and epithelial permeability, hypercoagulation and hypofibrinolysis, inflammation, and immune modulation. These detrimental changes are orchestrated by cross talk between a complex network of cells, mediators, and signaling pathways. A rapidly growing number of studies have reported the appearance of distinct populations of microparticles (MPs) in both the vascular and alveolar compartments in animal models of ALI/ARDS or respective patient populations, where they may serve as diagnostic and prognostic biomarkers. MPs are small cytosolic vesicles with an intact lipid bilayer that can be released by a variety of vascular, parenchymal, or blood cells and that contain membrane and cytosolic proteins, organelles, lipids, and RNA supplied from and characteristic for their respective parental cells. Owing to this endowment, MPs can effectively interact with other cell types via fusion, receptor-mediated interaction, uptake, or mediator release, thereby acting as intrinsic stimulators, modulators, or even attenuators in a variety of disease processes. This review summarizes current knowledge on the formation and potential functional role of different MPs in inflammatory diseases with a specific focus on ALI/ARDS. ALI has been associated with the formation of MPs from such diverse cellular origins as platelets, neutrophils, monocytes, lymphocytes, red blood cells, and endothelial and epithelial cells. Because of their considerable heterogeneity in terms of origin and functional properties, MPs may contribute via both harmful and beneficial effects to the characteristic pathological features of ALI/ARDS. A better understanding of the formation, function, and relevance of MPs may give rise to new promising therapeutic strategies to modulate coagulation, inflammation, endothelial function, and permeability either through removal or inhibition of "detrimental" MPs or through administration or stimulation of "favorable" MPs.
急性肺损伤（ALI）及其最严重形式急性呼吸窘迫综合征（ARDS）的病理生理学特征为血管和上皮通透性增加、高凝和低纤维蛋白溶解、炎症和免疫调节。这些有害变化是由细胞、介质和信号通路的复杂网络之间的相互作用协调的。越来越多的研究报告称，在 ALI/ARDS 的动物模型或相应的患者群体中，血管和肺泡隔室中都出现了独特的微粒（MP）群体，它们可能作为诊断和预后的生物标志物。MP 是带有完整脂质双层的小细胞浆囊泡，可以由多种血管、实质或血细胞释放，并且包含源自其亲代细胞的膜和细胞质蛋白、细胞器、脂质和 RNA。由于这种特性，MP 可以通过融合、受体介导的相互作用、摄取或介质释放有效地与其他细胞类型相互作用，从而在各种疾病过程中充当内在的刺激物、调节剂甚至衰减物。本综述总结了目前关于炎症性疾病中不同 MP 的形成和潜在功能作用的知识，重点是 ALI/ARDS。ALI 与来自血小板、中性粒细胞、单核细胞、淋巴细胞、红细胞以及内皮细胞和上皮细胞等多种细胞来源的 MPs 的形成有关。由于它们在起源和功能特性方面存在很大的异质性，因此 MPs 可能通过有害和有益的作用对 ALI/ARDS 的特征性病理特征产生影响。更好地了解 MPs 的形成、功能和相关性可能会产生新的有前途的治疗策略，通过去除或抑制“有害”MPs 或通过给予或刺激“有利”MPs 来调节凝血、炎症、内皮功能和通透性。
