Tong Shan, Wang Haibao, Zhang Ting, Chen Linfeng, Liu Bowei
Department of Blood Transfusion, The General Hospital of The People's Liberation Army, Beijing 100085, P.R. China.
Mol Med Rep. 2015 Nov;12(5):7777-81. doi: 10.3892/mmr.2015.4347. Epub 2015 Sep 22.
Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-associated morbidity and mortality. Activated platelets have important roles in TRALI and CD62P was identified to be an important indicator of platelet activation. However, the precise roles of CD62P in TRALI have remained elusive. The present study assessed CD62P accumulation during storage of apheresis platelet concentrates (A‑Plts) and established a mouse model of TRALI to further investigate the roles of CD62P in TRALI. The results showed that the CD62P concentration in A‑Plts was increased with the storage time. Mice were treated with monoclonal major histocompatibility complex (MHC)‑1 antibody to induce TRALI. The murine model of TRALI was successfully established as evidenced by pulmonary oedema, accompanied by decreased clearance of bronchoalveolar lavage fluid (BALF), increased pulmonary and systemic inflammation, elevated lung myeloperoxidase (MPO) activity as well as increased pulmonary and systemic coagulation in the TRALI group compared with those in the control group. To further determine the role of CD62P in TRALI, mice were treated with anti‑CD62P antibody to knockdown CD62P in vivo. It was found that pulmonary oedema, BALF clearance, pulmonary and systemic inflammation, MPO activity as well as pulmonary and systemic coagulation were decreased in the TRALI + anti‑CD62P antibody group compared with those in the TRALI + isotype antibody group. The present study supported the notion that CD62P is involved in mediating TRALI and may provide an important molecular basis for enhancing the clinical safety and effectiveness of platelet transfusion.
输血相关急性肺损伤(TRALI)是输血相关发病和死亡的主要原因。活化血小板在TRALI中起重要作用,并且CD62P被确定为血小板活化的重要指标。然而,CD62P在TRALI中的精确作用仍不清楚。本研究评估了单采血小板浓缩物(A-Plts)储存期间CD62P的积累情况,并建立了TRALI小鼠模型,以进一步研究CD62P在TRALI中的作用。结果显示,A-Plts中CD62P浓度随储存时间增加。用单克隆主要组织相容性复合体(MHC)-1抗体处理小鼠以诱导TRALI。与对照组相比,TRALI组出现肺水肿,伴有支气管肺泡灌洗液(BALF)清除率降低、肺和全身炎症增加、肺髓过氧化物酶(MPO)活性升高以及肺和全身凝血增加,从而成功建立了TRALI小鼠模型。为了进一步确定CD62P在TRALI中的作用,用抗CD62P抗体处理小鼠以在体内敲低CD62P。发现与TRALI+同型抗体组相比,TRALI+抗CD62P抗体组的肺水肿、BALF清除率、肺和全身炎症、MPO活性以及肺和全身凝血均降低。本研究支持CD62P参与介导TRALI这一观点,并可能为提高血小板输血的临床安全性和有效性提供重要的分子基础。