Fraser D G, Regal J F, Arndt M L
Toxicology Graduate Program, University of Minnesota, Duluth, USA.
J Pharmacol Exp Ther. 1995 May;273(2):793-801.
Trimellitic anhydride (TMA) is a small molecular weight industrial compound that will cause asthma-like symptoms in humans. Some of these TMA-induced symptoms can be reproduced in the guinea pig. In the guinea pig model of TMA-induced asthma, intratracheal instillation of TMA coupled to guinea pig serum albumin causes an immediate bronchoconstriction and increase in airway microvascular leakage with concomitant decrease in circulating platelets and white blood cells and subsequent cellular infiltration of mononuclear cells, neutrophils and eosinophils into the bronchoalveolar lavage fluid. In addition, in the lung tissue an increase in eosinophil peroxidase activity (a measure of eosinophil numbers) occurs. The purpose of this study was to determine whether complement system activation was essential for any of these TMA-induced events. Guinea pigs pretreated with cobra venom factor (CVF) had significantly reduced amounts of complement component C3 in the lavage fluid 24 hours after TMA conjugated to guinea pig serum albumin challenge indicating that the CVF treatment was successful in depleting complement proteins. Pretreatment with CVF did not affect the immediate TMA-induced bronchoconstriction nor the TMA-induced microvascular leakage. In animals depleted of the complement system by pretreatment with CVF the TMA-induced increase in mononuclear cells, total white blood cells, red blood cells, and EPO activity in the bronchoalveolar lavage was significantly reduced. Thus, our results suggest that in the guinea pig, the complement system is an important source of mediators for cellular infiltration into the lung after exposure to this acid anhydride and that inhibiting complement activation may be useful in preventing the inflammatory cell infiltration in TMA-induced asthma.
偏苯三酸酐（TMA）是一种分子量较小的工业化合物，可导致人类出现类似哮喘的症状。其中一些由TMA诱发的症状在豚鼠身上也能重现。在TMA诱发哮喘的豚鼠模型中，气管内滴注与豚鼠血清白蛋白偶联的TMA会导致立即出现支气管收缩，气道微血管渗漏增加，同时循环血小板和白细胞减少，随后单核细胞、中性粒细胞和嗜酸性粒细胞浸润到支气管肺泡灌洗液中。此外，肺组织中嗜酸性粒细胞过氧化物酶活性增加（嗜酸性粒细胞数量的一种度量）。本研究的目的是确定补体系统激活对于这些由TMA诱发的事件是否至关重要。用眼镜蛇毒因子（CVF）预处理的豚鼠在接受与豚鼠血清白蛋白偶联的TMA攻击24小时后，灌洗液中补体成分C3的量显著减少，这表明CVF处理成功地消耗了补体蛋白。用CVF预处理并不影响TMA立即诱发的支气管收缩，也不影响TMA诱发的微血管渗漏。在用CVF预处理使补体系统耗竭的动物中，TMA诱发的支气管肺泡灌洗中单核细胞、总白细胞、红细胞和EPO活性的增加显著减少。因此，我们的结果表明，在豚鼠中，补体系统是暴露于这种酸酐后细胞浸润到肺中的重要介质来源，抑制补体激活可能有助于预防TMA诱发哮喘中的炎症细胞浸润。
