该课题组人员发现，发现，在血流剪切作用下，血管性血友病因子或纤维蛋白与αIIbβ3结合可触发该蛋白聚集于血小板质膜延伸结构中，形成"血小板衍生整合素与四跨膜蛋白富集性膜丝"。PITTs能持续锚定于白细胞或内皮细胞表面，而部分缺失αIIbβ3的血小板主体则发生分离。缺乏αIIbβ3的血小板虽然仍对刺激有反应，但不支持血栓形成。在无主题感染和内毒素血症模型中，PITTs促进白细胞活化和血管炎症，αIIbβ3阻断可减轻免疫介导的组织损伤。在脓毒症、COVID-19或严重感染患者中，PITT形成和血小板αIIbβ3丢失与疾病严重程度和不良结局相关。该课题组人员认为PITTs是一种促炎结构，可以放大免疫反应，同时促进血栓炎性疾病中的血小板功能障碍。
研究人员表示，血小板整合素αIIbβ3对止血、血栓形成和炎症至关重要。
附：英文原文
Title: Platelet-derived integrin- and tetraspanin-enriched tethers exacerbate severe inflammation
Author: Charly Kusch, David Stegner, Lukas J. Weiss, Paquita Nurden, Philipp Burkard, Denise Johnson, Wolfgang Bergmeier, Ceylan Onursal, Stefano Navarro, Christian Hackenbroch, Dennis Pfeiffer, Sabrina Ivana Bonfiglio, Mara Meub, Carina Gross, Joachim Schenk, Valeria Fumagalli, Kristina Mott, Markus Bender, Matteo Iannacone, Oliver Andres, Wolfgang Kastenmüller, Katrin G. Heinze, Markus Sauer, Harald Schulze, Klaus Ley, Alan T. Nurden, Bernhard Nieswandt
Issue&Volume: 2026-01-22
Abstract: Platelet integrin αIIbβ3 is essential for hemostasis, thrombosis, and inflammation. We found that ligation of αIIbβ3 by von Willebrand factor or fibrin under flow triggered its accumulation in plasma membrane extensions or “platelet-derived integrin- and tetraspanin-enriched tethers” (PITTs). PITTs remained anchored to leukocytes or endothelial cells, whereas the partially αIIbβ3-deficient platelet body detached. Although still responsive to stimuli, αIIbβ3-deficient platelets did not support thrombus formation. PITTs promoted leukocyte activation and vascular inflammation in mouse models of infection and endotoxemia, and αIIbβ3 blockade reduced immune-mediated tissue damage. In patients with sepsis, COVID-19, or severe infections, PITT formation and platelet αIIbβ3 loss correlated with disease severity and adverse outcomes. We propose that PITTs are proinflammatory structures that amplify immune responses while contributing to platelet dysfunction in thrombo-inflammatory disease.
DOI: adu2825
Source: https://www.science.org/doi/10.1126/science.adu2825