Mulligan M S, Schmid E, Beck-Schimmer B, Till G O, Friedl H P, Brauer R B, Hugli T E, Miyasaka M, Warner R L, Johnson K J, Ward P A
Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
J Clin Invest. 1996 Jul 15;98(2):503-12. doi: 10.1172/JCI118818.
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 125I-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 TNFalpha 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 TNFalpha and the corresponding upregulation of lung vascular ICAM-1.
补体激活产物C5a可能在急性炎症反应中起关键作用。使用抗大鼠C5a的多克隆抗体来确定在通过眼镜蛇毒因子（CVF）全身激活补体后或在肺内沉积IgG免疫复合物后，中性粒细胞依赖性炎症性肺损伤中C5a的需求。在CVF模型中，静脉输注（而非气管内滴注）抗C5a可使肺通透性和肺髓过氧化物酶含量呈剂量依赖性降低。在C6缺陷大鼠中，输注CVF导致的肺损伤水平（通过125I-白蛋白渗漏测量）与C6充足大鼠中发现的相同。在IgG免疫复合物肺损伤模型中，气管内（而非静脉内）给予抗C5a可剂量依赖性地降低肺血管通透性增加以及肺髓过氧化物酶的积累。用抗C5a治疗可极大地抑制肺血管细胞间黏附分子-1（ICAM-1）的上调。这与支气管肺泡液中TNFα水平的大幅下降相关。这些数据证明了在两种损伤模型中对C5a的需求。在IgG免疫复合物模型中，C5a是TNFα充分产生以及肺血管ICAM-1相应上调所必需的。
