Clostridium perfringens phospholipase C-induced platelet/leukocyte interactions impede neutrophil diapedesis
Clostridium perfringens phospholipase C-induced platelet/leukocyte interactions impede neutrophil diapedesis
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DOI：
10.1099/jmm.0.46390-0
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发表时间：
2006-05-01
影响因子：
3
通讯作者：
Stevens, DL
中科院分区：
文献类型：
--
作者：
Bryant, AE;Bayer, CR;Stevens, DL
产气荚膜梭菌气性坏疽是一种暴发性坏死性感染，感染组织中明显没有炎症细胞，但常聚集在邻近血管内。研究表明，产气荚膜梭菌磷脂酶C （PLC）刺激血管内大的血小板/白细胞复合物的形成，PLC诱导的血小板活化起主要作用。在体内，这种聚集体有助于微血管血栓形成和组织缺血坏死。然而，粘附血小板对中性粒细胞淤积的影响尚未确定。本研究研究了(1)血小板p选择素（CD62P）在plc诱导的细胞复合体形成中的作用；(2)血小板粘附对中性粒细胞迁移的影响。采用流式细胞术和光镜观察抗gpllblla和抗cd62p策略对plc诱导复合物形成的影响。血小板gplblla和CD62P都有助于血小板/白细胞复合物的形成。具体来说，gplblla介导了主要通过CD62P连接到白细胞上的大血小板/血小板聚集体的形成。中性粒细胞淤积，通过跨内皮细胞迁移测定和电子显微镜观察，由于大血小板聚集体的粘附，明显减少（bbb60 %）。我们得出结论，产气荚膜梭菌气性坏疽没有组织炎症反应，部分原因是由于PLC诱导的大量粘附血小板引起的中性粒细胞流动性受损。此外，针对gpllblla和CD62P的辅助免疫治疗策略可以改善组织炎症反应，防止血管闭塞，维持组织活力，减少梭状芽胞杆菌气性坏疽患者根治性截肢的需要。
Clostridium perfringens gas gangrene is a fulminant necrotizing infection in which inflammatory cells are notably absent from infected tissues but are often massed within adjacent vessels. It has been shown that C. perfringens phospholipase C (PLC) stimulates formation of large intravascular platelet/leukocyte complexes and that PLC-induced activation of platelet gpllbllla plays a major role. In vivo, such aggregates contribute to microvascular thrombosis and ischaemic necrosis of tissue. However, the effects of adherent platelets on neutrophil diapedesis have not been established. The present work investigated (1) the contribution of platelet P-selectin (CD62P) to PLC-induced cellular complex formation and (2) the effects of platelet adhesion on neutrophil diapedesis. The effects of anti-gpllbllla and anti-CD62P strategies on PLC-induced complex formation were measured by flow cytometry and followed by light microscopy. Both platelet gpllbllla and CD62P contributed to the formation of platelet/leukocyte complexes. Specifically, gpllbllla mediated the formation of large platelet/platelet aggregates that were tethered to the leukocyte principally via CD62P. Neutrophil diapedesis, quantified by a transendothelial cell migration assay and visualized by electron microscopy, was significantly reduced (> 60%) by the adherence of large platelet aggregates. It was concluded that the absence of a tissue inflammatory response in C. perfringens gas gangrene is due, in part, to impaired neutrophil mobility caused by large aggregates of adherent platelets induced by PLC. Further, an adjunctive immunotherapeutic strategy targeting both gpllbllla and CD62P may improve the tissue inflammatory response, prevent vascular occlusion, maintain tissue viability, and reduce the need for radical amputation in patients with clostridial gas gangrene.