Circulating platelets as a source of the damage-associated molecular pattern HMGB1 in patients with systemic sclerosis
Circulating platelets as a source of the damage-associated molecular pattern HMGB1 in patients with systemic sclerosis
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DOI：
10.3109/08916934.2012.719946
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发表时间：
2012-12-01
期刊：
影响因子：
3.5
通讯作者：
Manfredi, Angelo A.
中科院分区：
文献类型：
--
作者：
Maugeri, Norma;Franchini, Stefano;Manfredi, Angelo A.
系统性硬化症（SSc）中血小板活化与血管损伤之间的联系尚不清楚。在这里，我们报道了血小板激活导致i)从细胞质到HMGB1表面的易位，这是一个与组织再生相关的典型DAMP信号，ii)表达HMGB1的血小板衍生微粒（PD mu P）的释放。与年龄匹配的健康对照（HC, n = 20）相比，SSc患者（n = 29）的循环血小板HMGB1含量降低（334.6 +/- 21.2 vs 587.1 +/- 11.1 AUF, P < 0.001）， HMGB1易位至质膜外小叶（17.8 +/- 3.5 vs 4.5 +/- 0.5%, P < 0.001）。相反，SSc患者血液中PDmP的比例明显更高，而HC患者则没有（HMGB1）持续暴露（MFI 62.8 +/- 3.95 vs 4.3 +/- 0.7）。SSc患者的血小板HMGB1缺失与脱颗粒、p -选择素和组织因子的表达以及纤维蛋白原与质膜结合显著相关。这些发现表明，血小板是SSc患者血管中HMGB1的来源，HMGB1是坏死的祖先信号，可能导致持续的微血管损伤和内皮细胞活化。
The link between platelet activation and vascular injury in Systemic Sclerosis (SSc) is poorly characterized. Here we report that platelet activation results in i) the translocation from the cytoplasm to the surface of HMGB1, a prototypical DAMP signal associated with tissue regeneration and ii) the release of platelet derived microparticles (PD mu P) expressing HMGB1. Decreased HMGB1 content (334.6 +/- 21.2 vs 587.1 +/- 11.1 AUF, P < 0.001) and HMGB1 translocation to the outer leaflet of the plasma membrane (17.8 +/- 3.5 vs 4.5 +/- 0.5%, P < 0.001) characterize circulating platelets of SSc patients (n = 29) when compared with age-matched healthy controls (HC, n = 20). Conversely, a significantly higher fraction of PDmP in the blood of SSc patients, but not of HC, consistently expose (HMGB1 (MFI 62.8 +/- 3.95 vs 4.3 +/- 0.7). Platelet HMGB1 depletion is significantly associated in SSc patients with degranulation and with expression of P-selectin and of tissue factor as well as with fibrinogen binding to their plasma membrane. These findings indicate that platelets represent a source of HMGB1, an ancestral signal of necrosis, in the vasculature of SSc patients, possible contributing to persistent microvascular injury and endothelial cell activation.