7/31/2023 0 Comments Front mission 2089 apj![]() ![]() In patients with severe COVID-19 who suffered from acute activation of complement triggered by severe acute respiratory syndrome coronavirus 2 infection, we found the same C5a-dependent pathogenic mechanisms. ![]() Mechanistic studies showed that C5a caused RalA-mediated exocytosis of von Willebrand factor (vWF) and P-selectin from Weibel-Palade bodies, which favored further vWF binding on the endothelium and platelet adhesion and aggregation. C5a added to normal human serum fully recapitulated the prothrombotic effects of aHUS serum. In vitro and ex vivo assays with serum from patients with atypical hemolytic uremic syndrome (aHUS), a prototype rare disease of complement-mediated microvascular thrombosis due to genetically determined alternative pathway dysregulation, and cultured microvascular endothelial cells, demonstrated that the C5a/C5aR1 axis is a key player in endothelial thromboresistance loss. The aim of this study was to investigate the role of the C5a/C5aR1 axis as opposed to C5b-9 in inducing endothelial dysfunction and loss of antithrombogenic properties. In endothelial cells, complement hyperactivation may translate into cell dysfunction, favoring thrombus formation. Unrestrained activation of the complement system till the terminal products, C5a and C5b-9, plays a pathogenetic role in acute and chronic inflammatory diseases. Sistiana Aiello, Sara Gastoldi, Miriam Galbusera, Piero Ruggenenti, Valentina Portalupi, Stefano Rota, Nadia Rubis, Lucia Liguori, Sara Conti, Matteo Tironi, Sara Gamba, Donata Santarsiero, Ariela Benigni, Giuseppe Remuzzi, Marina Noris, Sistiana Aiello, Sara Gastoldi, Miriam Galbusera, Piero Ruggenenti, Valentina Portalupi, Stefano Rota, Nadia Rubis, Lucia Liguori, Sara Conti, Matteo Tironi, Sara Gamba, Donata Santarsiero, Ariela Benigni, Giuseppe Remuzzi, Marina Noris Abstract ![]()
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