Xie Ru Feng, Hu Ping, Wang Zhi Cheng, Yang Jie, Yang Yi Ming, Gao Li, Fan Hua Hua, Zhu Yong Ming
Shanghai Blood Center, Shanghai, China.
The Institute of Life Science, East China Normal University, Shanghai, China.
Transfusion. 2015 May;55(5):1051-7. doi: 10.1111/trf.12952. Epub 2015 Jan 6.
Platelets (PLTs) stored at 22°C accumulate microparticles and biologic response modifiers (BRMs) that induce inflammatory reactions in transfusion recipients. However, soluble BRMs are fully diluted in the recipient's blood circulation. The mechanisms by which BRMs exert their effects have not been elucidated. The objectives of this study were to determine the effect of PLT microparticles (PMPs) on polymorphonuclear leukocyte (PMN)-mediated human pulmonary microvascular endothelial cell (HMVEC) damage and determine the role of soluble CD40 ligand (sCD40L).
PMPs were isolated from apheresis PLT concentrates. We used a two-insult in vitro model of HMVEC damage to investigate the effects of PMP and sCD40L and role of apocynin, an inhibitor of PMN respiratory burst. Their priming activities were measured using hydrogen peroxide production. The expression of intercellular cell adhesion molecule-1 (ICAM-1) and integrin αM (CD11b) were also determined.
Lipopolysaccharide (LPS)-activated HMVEC damage and PMN respiratory burst depend on the presence of PMP and the concentration of sCD40L. PMP-induced PMN-mediated HMVEC damage was significantly reduced by apocynin-treated PMNs (p < 0.05). The surface expression of ICAM-1 on HMVEC was increased by LPS stimulation. The expression of CD11b on PMNs was increased by PMP priming. Blocking ICAM-1 with a monoclonal antibody (MoAb) CD54 significantly reduced HMVEC damage (p < 0.05). The treatment of endothelial cells but not PMN with a MoAb targeting CD40 failed to prevent the HMVEC damage caused by PMPs (p > 0.05).
PMPs carry a concentrated CD40L signal, promote PMN-mediated HMVEC damage, and may affect the development of transfusion-related acute lung injury.
储存在22°C的血小板（PLT）会积累微粒和生物反应调节剂（BRM），这些物质会在输血受者体内引发炎症反应。然而，可溶性BRM会在受者的血液循环中被完全稀释。BRM发挥作用的机制尚未阐明。本研究的目的是确定血小板微粒（PMP）对多形核白细胞（PMN）介导的人肺微血管内皮细胞（HMVEC）损伤的影响，并确定可溶性CD40配体（sCD40L）的作用。
从单采血小板浓缩物中分离出PMP。我们使用HMVEC损伤的双打击体外模型来研究PMP和sCD40L的作用以及阿扑吗啡（一种PMN呼吸爆发抑制剂）的作用。使用过氧化氢产生量来测量它们的启动活性。还测定了细胞间黏附分子-1（ICAM-1）和整合素αM（CD11b）的表达。
脂多糖（LPS）激活的HMVEC损伤和PMN呼吸爆发取决于PMP的存在和sCD40L的浓度。阿扑吗啡处理的PMN可显著降低PMP诱导的PMN介导的HMVEC损伤（p < 0.05）。LPS刺激可增加HMVEC上ICAM-1的表面表达。PMP启动可增加PMN上CD11b的表达。用单克隆抗体（MoAb）CD54阻断ICAM-1可显著降低HMVEC损伤（p < 0.05）。用靶向CD40的MoAb处理内皮细胞而非PMN未能预防PMPs引起的HMVEC损伤（p > 0.05）。
PMP携带浓缩的CD40L信号，促进PMN介导的HMVEC损伤，并可能影响输血相关急性肺损伤的发生发展。
