Sahler J, Spinelli S, Phipps R, Blumberg N
Department of Microbiology and Immunology, School of Medicine and Dentistry, University of Rochester, 601, Elmwood Avenue Rochester, New York 14642, USA.
Transfus Clin Biol. 2012 Jun;19(3):98-103. doi: 10.1016/j.tracli.2012.02.003. Epub 2012 Jun 14.
Platelet transfusions are commonly used treatments that occasionally lead to adverse reactions. Clinical trials, in vitro and animal studies have been performed to try to understand the causes of such reactions. Multiple studies have shown that the supernatant fraction of platelet concentrates contain prothrombotic and pro-inflammatory mediators. The origin of these mediators was first ascribed to white blood cells contaminating the platelet preparation. However, the accumulation of bioactive mediators after leukoreduction focused attention on platelets themselves during storage. Numerous cytokines, chemokines and prostaglandins are released in stored platelet concentrates. We have focused on a powerful mediator called soluble CD40 ligand (sCD40L, formally known as CD154) as a seminal contributor to adverse reactions. sCD40L can bind and signal the surface receptor, CD40, which is present on various types of human cells including white blood cells, vascular cells and fibroblasts. Downstream results of sCD40L/CD40 signaling include pro-inflammatory cytokine and chemokine production, prothrombotic mediator release, adherence and transmigration of leukocytes to endothelium and other undesirable vascular inflammatory events. Increased plasma levels of sCD40L can be detected in conditions such as myocardial infarction, stroke, unstable angina, high cholesterol, or other cardiovascular conditions. In retrospective studies, correlations were made between increased sCD40L levels of platelet concentrates and adverse transfusion reactions. We hypothesize that transfusion of partially activated, CD40L-expressing platelets along with sCD40L into a recipient with damaged or dysfunctional vascular tissue results in a "double-hit", thus inciting inflammation and vascular damage in the recipient.
血小板输注是常用的治疗方法，但偶尔会导致不良反应。已经进行了临床试验、体外研究和动物研究，试图了解此类反应的原因。多项研究表明，血小板浓缩物的上清液部分含有促血栓形成和促炎介质。这些介质的来源最初被归因于污染血小板制剂的白细胞。然而，白细胞去除后生物活性介质的积累使人们将注意力集中在储存过程中的血小板自身。在储存的血小板浓缩物中会释放出许多细胞因子、趋化因子和前列腺素。我们将重点放在一种名为可溶性CD40配体（sCD40L，正式名称为CD154）的强大介质上，认为它是不良反应的一个重要促成因素。sCD40L可以结合并向表面受体CD40发出信号，CD40存在于包括白细胞、血管细胞和成纤维细胞在内的各种人类细胞上。sCD40L/CD40信号传导的下游结果包括促炎细胞因子和趋化因子的产生、促血栓形成介质的释放、白细胞向内皮的粘附和迁移以及其他不良的血管炎症事件。在心肌梗死、中风、不稳定型心绞痛、高胆固醇或其他心血管疾病等情况下，可以检测到血浆中sCD40L水平升高。在回顾性研究中，血小板浓缩物中sCD40L水平升高与不良输血反应之间存在相关性。我们假设，将部分活化的、表达CD40L的血小板与sCD40L一起输注到血管组织受损或功能失调的受血者体内会导致“双重打击”，从而引发受血者体内的炎症和血管损伤。
