Vasina Elena M, Cauwenberghs Sandra, Staudt Mareike, Feijge Marion Ah, Weber Christian, Koenen Rory R, Heemskerk Johan Wm
Institute for Molecular Cardiovascular Research (IMCAR), University Hospital Aachen, Medical Faculty, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen Germany ; Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Maastricht, the Netherlands.
Am J Blood Res. 2013 May 5;3(2):107-23. Print 2013.
Platelet microparticles (PM) are the most abundant cell-derived microparticles in the blood, and accumulate in thrombo-inflammatory diseases. Platelets produce PM upon aging via an apoptosis-like process and by activation with strong agonists. We previously showed that long-term treatment of monocytic cells with apoptosis-induced PM (PMap) promotes their differentiation into resident macrophages. Here we investigated shorter term effects of various types of PM on monocyte signalling and function.
Flow cytometry and scanning electron microscopy revealed that PM formed upon platelet aging (PMap) or ultra-sonication (PMsonic) expressed activated αIIbβ3 integrins and tended to assemble into aggregates. In contrast, PM formed upon platelet activation with thrombin (PMthr) or Ca(2+) ionophore (PMiono) had mostly non-activated αIIbβ3 and little aggregate formation, but had increased CD63 expression. PM from activated and sonicated platelets expressed phosphatidylserine at their surface, while only the latter were enriched in the receptors CD40L and CX3CR1. All PM types expressed P-selectin, interacted with monocytic cells via this receptor, and were internalised into these cells. The various PM types promoted actin cytoskeletal rearrangements and hydrogen peroxide production by monocytic cells. Markedly, both aging- and activation-induced PM types stimulated the phosphoinositide 3-kinase/Akt pathway, suppressing apoptosis induced by several agonists, in a P-selectin-dependent manner. On the other hand, the PM types differentially influenced monocyte signalling in eliciting Ca(2+) fluxes (particularly PMap) and in releasing secondary mediators (complement factor C5a with PMap, and pro-inflammatory tumour necrosis factor-α with PMthr).
In spite of their common anti-apoptotic potential via Akt activation, aging- and activation-induced PM cause different Ca(2+) signalling events and mediator release in monocytic cells. By implication, aging and activated platelets may modulate monocyte function in different way by the shedding of different PM types.
血小板微粒（PM）是血液中最丰富的细胞衍生微粒，在血栓炎症性疾病中会积聚。血小板在老化时通过类似凋亡的过程以及用强效激动剂激活后产生PM。我们之前表明，用凋亡诱导的PM（PMap）长期处理单核细胞可促进其分化为驻留巨噬细胞。在此，我们研究了不同类型PM对单核细胞信号传导和功能的短期影响。
流式细胞术和扫描电子显微镜显示，血小板老化（PMap）或超声处理（PMsonic）形成的PM表达活化的αIIbβ3整合素，并倾向于聚集成聚集体。相比之下，用凝血酶（PMthr）或Ca(2+)离子载体（PMiono）激活血小板形成的PM大多具有未活化的αIIbβ3且很少形成聚集体，但CD63表达增加。活化和超声处理的血小板产生的PM在其表面表达磷脂酰丝氨酸，而只有后者富含受体CD40L和CX3CR1。所有类型的PM均表达P-选择素，通过该受体与单核细胞相互作用，并被内化到这些细胞中。不同类型的PM促进单核细胞的肌动蛋白细胞骨架重排和过氧化氢产生。值得注意的是，老化和激活诱导的PM类型均以P-选择素依赖性方式刺激磷酸肌醇3-激酶/蛋白激酶B（PI3K/Akt）途径，抑制几种激动剂诱导的细胞凋亡。另一方面，不同类型的PM在引发Ca(2+)通量（特别是PMap）和释放次级介质（PMap释放补体因子C5a，PMthr释放促炎性肿瘤坏死因子-α）方面对单核细胞信号传导有不同影响。
尽管老化和激活诱导的PM通过Akt激活具有共同的抗凋亡潜力，但它们在单核细胞中引起不同的Ca(2+)信号事件和介质释放。这意味着，老化和活化的血小板可能通过释放不同类型的PM以不同方式调节单核细胞功能。
