In Vitro and In Vivo Characterization of Ultraviolet Light C-Irradiated Human Platelets in a 2 Event Mouse Model of Transfusion

UV-based pathogen reduction technologies have been developed in recent years to inactivate pathogens and contaminating leukocytes in platelet transfusion products in order to prevent transfusion-transmitted infections and alloimmunization. UVC-based technology differs from UVA or UVB-based technologies in that it uses a specific wavelength at 254 nm without the addition of any photosensitizers. Previously, it was reported that UVC irradiation induces platelet aggregation and activation. To understand if UVC-induced changes of platelet quality correlate with potential adverse events when these platelets are transfused into animals, we used a 2-event SCID mouse model in which the predisposing event was LPS treatment and the second event was infusion of UVC-irradiated platelets. We analyzed lung platelet accumulation, protein content in bronchoalveolar lavage fluid as an indication of lung injury, and macrophage inflammatory protein-2 (MIP-2) release in mice received UVC-irradiated or untreated control platelets. Our results showed UVC-irradiated platelets accumulated in lungs of the mice in a dose-dependent manner. High-doses of UVC-irradiated platelets were sequestered in the lungs to a similar level as we previously reported for UVB-irradiated platelets. Unlike UVB-platelets, UVC-platelets did not lead to lung injury or induce MIP-2 release. This could potentially be explained by our observation that although UVC treatment activated platelet surface αIIbβ3, it failed to activate platelet cells. It also suggests lung platelet accumulation and subsequent lung damage are due to different and separate mechanisms which require further investigation.

近年来，基于紫外线（UV）的病原体灭活技术已被研发问世，用于灭活血小板输注制品中的病原体与污染白细胞，以预防输血传播感染及同种免疫反应。紫外线C（UVC）基技术与紫外线A（UVA）、紫外线B（UVB）基技术存在差异：其采用254 nm的特定波长，且无需添加任何光敏剂。此前已有研究表明，UVC照射可诱导血小板聚集与活化。为探究UVC诱导的血小板质量变化与输注动物后可能出现的不良事件是否相关，我们采用了双事件重症联合免疫缺陷（SCID）小鼠模型：造模的首要事件为脂多糖（LPS）处理，次要事件为输注UVC照射后的血小板。我们对输注UVC照射血小板或未处理对照血小板的小鼠展开分析，检测了肺部血小板聚集情况、作为肺损伤指标的支气管肺泡灌洗液蛋白含量，以及巨噬细胞炎性蛋白2（MIP-2）的释放水平。研究结果显示，UVC照射后的血小板会以剂量依赖的方式在小鼠肺部聚集。高剂量UVC照射血小板在肺部的截留水平，与我们此前报道的UVB照射血小板截留水平相当。与UVB照射血小板不同，UVC照射血小板不会引发肺损伤，也不会诱导MIP-2释放。这一现象可通过我们的观测结果得到解释：尽管UVC处理可激活血小板表面的αIIbβ3，但无法完全活化血小板细胞。该结果同时提示，肺部血小板聚集与后续肺损伤的发生机制存在差异且相互独立，有待进一步研究探明。