Meziani Ferhat, Tesse Angela, Andriantsitohaina Ramaroson
Centre National de la Recherche Scientifique/UMR, Angers, France.
Pharmacol Rep. 2008 Jan-Feb;60(1):75-84.
Both inflammation and thrombosis can be orchestrated by the interactions between circulating cells, such as leukocytes and platelets, with vascular, endothelial and smooth muscle cells, which, during activation or apoptosis, can release circulating microparticles (MPs). Indeed, MPs are membrane vesicles with procoagulant and proinflammatory properties. MPs are present in blood from healthy individuals and in patients under several pathological states, for instance sepsis, preeclampsia, Crohn's disease and diabetes, strengthening the notion that MPs may play a role in these diseases. Circulating MPs or those generated in vitro from apoptotic T cells display deleterious effects on endothelial and/or vasomotor function. In contrast, MPs might be protective to endothelial cells. We have shown that MPs harboring the morphogen sonic hedgehog may represent a new therapeutic approach against endothelial dysfunction during acute severe endothelial injury. Indeed, these types of MPs induce NO release, decrease production of reactive oxygen species and induce angiogenesis from endothelial cells. This protective role for the endothelium was confirmed also by their in vivo injection in mice in which they were also able to reverse endothelial dysfunction in a model of heart ischemia/reperfusion. On the contrary, MPs from preeclamptic women compared to those from normal pregnant women showed pro-inflammatory properties in the vascular wall inducing vascular hyporeactivity in vessels from humans and mice. These effects were associated with complex interactions between NO and cyclooxygenase systems via endothelial cell activation. Altogether, these findings suggest that MPs can be considered as vectors of biological messages for vascular homeostasis, during immunity and inflammation.
炎症和血栓形成都可能由循环细胞(如白细胞和血小板)与血管、内皮细胞和平滑肌细胞之间的相互作用所调控,这些细胞在激活或凋亡过程中可释放循环微粒(MPs)。实际上,MPs是具有促凝和促炎特性的膜囊泡。MPs存在于健康个体的血液以及处于多种病理状态(如败血症、先兆子痫、克罗恩病和糖尿病)的患者血液中,这强化了MPs可能在这些疾病中发挥作用的观点。循环MPs或由凋亡T细胞体外产生的MPs对内皮和/或血管舒缩功能具有有害影响。相比之下,MPs可能对内皮细胞具有保护作用。我们已经表明,携带形态发生素音猬因子的MPs可能代表一种针对急性严重内皮损伤期间内皮功能障碍的新治疗方法。事实上,这类MPs可诱导一氧化氮(NO)释放,减少活性氧的产生,并诱导内皮细胞生成血管。通过在小鼠体内注射这些MPs也证实了它们对内皮的这种保护作用,在心脏缺血/再灌注模型中,它们还能够逆转内皮功能障碍。相反,与正常孕妇来源的MPs相比,先兆子痫孕妇的MPs在血管壁中表现出促炎特性,可导致人和小鼠血管反应性降低。这些效应与通过内皮细胞激活的NO和环氧化酶系统之间的复杂相互作用有关。总之,这些发现表明,MPs可被视为在免疫和炎症过程中维持血管稳态的生物信息载体。