Khoy Kathy, Nguyen Minh Vu Chuong, Masson Dominique, Bardy Béatrice, Drouet Christian, Paclet Marie-Hélène
GREPI EA 7408, Université Grenoble Alpes, Grenoble, France.
Université de Caen Normandie, CHU Caen, Caen, France.
Transfusion. 2017 Jul;57(7):1699-1708. doi: 10.1111/trf.14134. Epub 2017 Jun 13.
Transfusion-related acute lung injury (TRALI) is a major complication of hemotherapy that may occur after the transfusion of any blood type component. Several clinical reports have suggested the presence of anti-HLA antibodies in the blood product. This study sought to examine the role of anti-HLA-A2 antibodies in polymorphonuclear neutrophil (PMN) activation and thus in endothelial permeability.
PMN activation was assessed by both nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) activity and reactive oxygen species (ROS) production. A coculture assay of EA.hy926 endothelial cells with PMNs or differentiated-PLB-985 cells, a model of neutrophil-like cells, was performed to estimate the impact of ROS on endothelial permeability.
Anti-HLA-A2 antibodies significantly increased PMN activation, with subsequent endothelial dysfunction. Phagocyte NADPH oxidase (NOX2) activity was shown to be involved in this process and ROS themselves were demonstrated to induce VE-cadherin cleavage and endothelial permeability.
Our data may support the existence of a critical anti-HLA-A2 antibody threshold for PMN activation, with NOX2 activity and subsequent endothelial permeability in the two-hit model of TRALI.
输血相关急性肺损伤（TRALI）是血液治疗的一种主要并发症，可发生于任何血型成分输血后。多项临床报告提示血液制品中存在抗HLA抗体。本研究旨在探讨抗HLA - A2抗体在多形核中性粒细胞（PMN）激活以及内皮通透性方面的作用。
通过烟酰胺腺嘌呤二核苷酸磷酸氧化酶（NADPH氧化酶）活性和活性氧（ROS）生成来评估PMN激活。进行EA.hy926内皮细胞与PMN或分化的PLB - 985细胞（一种中性粒细胞样细胞模型）的共培养试验，以评估ROS对内皮通透性的影响。
抗HLA - A2抗体显著增加PMN激活，随后导致内皮功能障碍。吞噬细胞NADPH氧化酶（NOX2）活性参与了这一过程，并且ROS本身被证明可诱导VE - 钙黏蛋白裂解和内皮通透性增加。
我们的数据可能支持在TRALI的双打击模型中，存在一个导致PMN激活、NOX2活性及随后内皮通透性增加的关键抗HLA - A2抗体阈值。
