Medizinische Klinik und Poliklinik I, Ludwig-Maximilians-Universität, 81377 Munich, Germany; Deutsches Zentrum für Herz-Kreislaufforschung (DZHK), 13347 Berlin, Germany.
Medizinische Klinik und Poliklinik I, Ludwig-Maximilians-Universität, 81377 Munich, Germany.
Cell. 2017 Nov 30;171(6):1368-1382.e23. doi: 10.1016/j.cell.2017.11.001.
Blood platelets are critical for hemostasis and thrombosis and play diverse roles during immune responses. Despite these versatile tasks in mammalian biology, their skills on a cellular level are deemed limited, mainly consisting in rolling, adhesion, and aggregate formation. Here, we identify an unappreciated asset of platelets and show that adherent platelets use adhesion receptors to mechanically probe the adhesive substrate in their local microenvironment. When actomyosin-dependent traction forces overcome substrate resistance, platelets migrate and pile up the adhesive substrate together with any bound particulate material. They use this ability to act as cellular scavengers, scanning the vascular surface for potential invaders and collecting deposited bacteria. Microbe collection by migrating platelets boosts the activity of professional phagocytes, exacerbating inflammatory tissue injury in sepsis. This assigns platelets a central role in innate immune responses and identifies them as potential targets to dampen inflammatory tissue damage in clinical scenarios of severe systemic infection.
血小板对于止血和血栓形成至关重要,并在免疫反应中发挥多种作用。尽管在哺乳动物生物学中有这些多样化的任务,但它们在细胞水平上的技能被认为是有限的,主要包括滚动、黏附和聚集形成。在这里,我们发现了血小板的一个未被重视的功能,并表明黏附的血小板使用黏附受体在其局部微环境中机械探测黏附基质。当肌动球蛋白依赖性牵引力克服基质阻力时,血小板迁移并将黏附基质与任何结合的颗粒物质一起堆积起来。它们利用这种能力作为细胞清道夫,扫描血管表面以寻找潜在的入侵者并收集沉积的细菌。迁移的血小板对微生物的收集增强了专业吞噬细胞的活性,加剧了败血症中炎症性组织损伤。这赋予了血小板在先天免疫反应中的核心作用,并将其确定为在严重全身感染的临床情况下减轻炎症性组织损伤的潜在靶点。