Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Am J Transplant. 2021 Mar;21(3):993-1002. doi: 10.1111/ajt.16231. Epub 2020 Sep 4.
In brain-dead donors immunological activation occurs, which deteriorates donor lung quality. Whether the complement system is activated and which pathways are herein involved, remain unknown. We aimed to investigate whether brain death (BD)-induced lung injury is complement dependent and dissected the contribution of the complement activation pathways. BD was induced and sustained for 3 hours in wild-type (WT) and complement deficient mice. C3 mice represented total complement deficiency, C4 mice represented deficiency of the classical and lectin pathway, and factor properdin (P) mice represented alternative pathway deficiency. Systemic and local complement levels, histological lung injury, and pulmonary inflammation were assessed. Systemic and local complement levels were reduced in C3 mice. In addition, histological lung injury and inflammation were attenuated, as corroborated by influx of neutrophils and gene expressions of interleukin (IL)-6, IL-8-like KC, TNF-α, E-selectin, and MCP-1. In C4 mice, complement was reduced on both systemic and local levels and histological lung injury and inflammatory status were ameliorated. In P mice, histological lung injury was attenuated, though systemic and local complement levels, IL-6 and KC gene expressions, and neutrophil influx were not affected. We demonstrated that BD-induced lung injury is complement dependent, with a primary role for the classical/lectin activation pathway.
在脑死亡供体中会发生免疫激活，这会降低供体肺的质量。补体系统是否被激活以及涉及哪些途径尚不清楚。我们旨在研究脑死亡（BD）诱导的肺损伤是否依赖补体，并剖析补体激活途径的贡献。在野生型（WT）和补体缺陷小鼠中诱导并持续 3 小时的 BD。C3 小鼠代表总补体缺陷，C4 小鼠代表经典和凝集素途径缺陷，以及因子properdin（P）小鼠代表替代途径缺陷。评估了系统和局部补体水平、组织学肺损伤和肺炎症。C3 小鼠的系统和局部补体水平降低。此外，组织学肺损伤和炎症减轻，这得到了中性粒细胞浸润和白细胞介素（IL）-6、IL-8 样 KC、TNF-α、E-选择素和 MCP-1 的基因表达的证实。在 C4 小鼠中，系统和局部补体水平降低，组织学肺损伤和炎症状态得到改善。在 P 小鼠中，组织学肺损伤减轻，尽管系统和局部补体水平、IL-6 和 KC 基因表达以及中性粒细胞浸润不受影响。我们证明 BD 诱导的肺损伤依赖补体，经典/凝集素激活途径起主要作用。
