Requirement and role of C5a in acute lung inflammatory injury in rats
Requirement and role of C5a in acute lung inflammatory injury in rats
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DOI：
10.1172/jci118818
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发表时间：
1996-07-15
影响因子：
15.9
通讯作者：
Ward, PA
中科院分区：
文献类型：
--
作者：
Mulligan, MS;Schmid, E;Ward, PA
补体激活产物C5a可能在急性炎症反应中起关键作用。采用抗大鼠C5a多克隆抗体，确定补体被眼镜蛇毒因子（cobra venom factor， CVF）全身激活或肺内IgG免疫复合物沉积后中性粒细胞依赖性炎症性肺损伤对C5a的需求。在CVF模型中，静脉输注（而非气管内灌注）抗c5a使肺通透性和髓过氧化物酶肺含量呈剂量依赖性降低。在c6缺乏的大鼠中，CVF输注引起与c6充足大鼠相同水平的肺损伤（通过i -125白蛋白泄漏来测量）。在肺损伤的IgG免疫复合物模型中，气管内给药（而不是静脉注射）抗c5a以剂量依赖的方式降低肺血管通透性的增加以及肺髓过氧化物酶的积累。抗c5a治疗可显著抑制肺血管细胞间粘附分子-1 （ICAM-1）的上调。这与支气管肺泡液中TNF α水平的大幅下降有关。这些数据证明了两种损伤模型对C5a的要求。在IgG免疫复合物模型中，C5a是TMF α充分产生和相应的肺血管ICAM-1上调所必需的。
The complement activation product, C5a, may play a key role in the acute inflammatory response. Polyclonal antibody to rat C5a was used to define the requirements for C5a in neutrophil-dependent inflammatory lung injury after systemic activation of complement by cobra venom factor (CVF) or after intrapulmonary deposition of IgG immune complexes. In the CVF model, intravenous infusion (but not intratracheal instillation) of anti-C5a produced a dose-dependent reduction in lung permeability and in lung content of myeloperoxidase. In C6-deficient rats, CVF infusion caused the same level of lung injury (measured by leak of I-125-albumin) as found in C6-sufficient rats. In the IgG immune complex model of lung injury, anti-C5a administered intratracheally (but not intravenously) reduced in a dose-dependent manner both the increase in lung vascular permeability as well as the buildup of lung myeloperoxidase. Treatment with anti-C5a greatly suppressed upregulation of lung vascular intercellular adhesion molecule-1 (ICAM-1). This was correlated with a substantial drop in levels of TNF alpha in bronchoalveolar fluids. These data demonstrate the requirement for C5a in the two models of injury. In the IgG immune complex model, C5a is required for the full production of TMF alpha and the corresponding upregulation of lung vascular ICAM-1.