Department of Intensive Care Medicine and Laboratory of Experimental Intensive Care and Anesthesiology (LEICA), Academic Medical Center, Amsterdam, the Netherlands.
Vox Sang. 2014 Jul;107(1):71-5. doi: 10.1111/vox.12128. Epub 2013 Dec 27.
Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related morbidity and mortality. Specific therapy is lacking. We assessed whether C1-inhibitor attenuates lung injury in a 'two-hit' TRALI model.
Mice were primed with lipopolysaccharide, subsequently TRALI was induced by MHC-I antibodies. In the intervention group, C1-inhibitor was infused concomitantly. Mice were supported with mechanical ventilation. After 2 h, mice were killed, lungs were removed and bronchoalveolar lavage fluid (BALF) was obtained.
Injection of MHC-I antibodies induced TRALI, illustrated by an increase in wet-to-dry ratio of the lungs, in BALF protein levels and in lung injury scores. TRALI was further characterized by complement activation, demonstrated by increased BALF levels of C3a and C5a. Administration of C1-inhibitor resulted in increased pulmonary C1-inhibitor levels with high activity. C1-inhibitor reduced pulmonary levels of complement C3a associated with improved lung injury scores. However, levels of pro-inflammatory mediators were unaffected.
In a murine model of TRALI, C1-inhibitor attenuated pulmonary levels of C3a associated with improved lung injury scores, but with persistent high levels of inflammatory cytokines.
输血相关急性肺损伤（TRALI）是输血相关发病率和死亡率的主要原因。目前缺乏特定的治疗方法。我们评估了 C1 抑制剂是否可以减轻“双打击”TRALI 模型中的肺损伤。
用脂多糖对小鼠进行预处理，随后用 MHC-I 抗体诱导 TRALI。在干预组中，同时输注 C1 抑制剂。对小鼠进行机械通气支持。2 小时后，处死小鼠，取出肺脏，收集支气管肺泡灌洗液（BALF）。
注射 MHC-I 抗体诱导了 TRALI，表现为肺湿重/干重比增加、BALF 蛋白水平升高和肺损伤评分增加。TRALI 还伴有补体激活，表现为 BALF 中 C3a 和 C5a 水平升高。给予 C1 抑制剂可导致肺组织中 C1 抑制剂水平升高且具有高活性。C1 抑制剂降低了与肺损伤评分改善相关的补体 C3a 的肺水平，但对促炎介质水平没有影响。
在 TRALI 的小鼠模型中，C1 抑制剂可降低与肺损伤评分改善相关的补体 C3a 的肺水平，但同时炎症细胞因子的水平持续较高。
