Fraser D G, Graziano F M, Larsen C P, Regal J F
Toxicology Graduate Program, University of Minnesota, Duluth 55812, USA.
Toxicol Appl Pharmacol. 1998 Jun;150(2):218-27. doi: 10.1006/taap.1998.8419.
Trimellitic anhydride (TMA) is a small molecular weight chemical used in the paint and plastics industry that can cause asthma-like symptoms in humans. Guinea pigs sensitized intradermally with TMA will respond to antigen challenge with asthma-like symptoms, including an immediate bronchoconstriction and a delayed cellular infiltration into the lung, particularly eosinophil infiltration. Sensitized guinea pigs produce TMA-specific IgG1, which is thought to be important in asthmatic reactions in this animal model; however, they also produce TMA-specific IgG2 antibody. The purpose of the present study was to determine the role of IgG1 and IgG2 in the TMA-induced immediate bronchoconstriction and delayed cellular infiltration in the guinea pig. Guinea pigs were passively sensitized by intratracheal instillation of TMA-specific IgG2, an antibody preparation enriched with TMA-specific IgG1, or a combination of the two. The allergic response was induced by intratracheal instillation of TMA conjugated to guinea pig serum albumin (TMA-GPSA). A significantly greater bronchoconstrictor response was observed in animals sensitized with a combination of the IgG2 and IgG1 preparation compared to those sensitized with IgG2 or the IgG1 preparation alone. Cellular infiltration was quantified 24 h after antigen challenge by differential cell counts of bronchoalveolar lavage (BAL) cells as well as by using eosinophil peroxidase (EPO) and myeloperoxidase (MPO) activity as a measure of the numbers of eosinophils and neutrophils, respectively. In the BAL, passively sensitizing with IgG2 alone resulted in an increase in both TMA-induced MPO and EPO activity. In contrast, in the lung, passively sensitizing with a partially purified preparation of TMA-specific IgG1 alone resulted in a significant increase in TMA-induced EPO activity. Passively sensitizing with IgG2 in conjunction with the IgG1 preparation resulted in an enhanced cellular infiltration and lung injury over that seen with either antibody preparation alone. These data demonstrate an augmentation of IgG1-mediated responses by the addition of IgG2 and suggest a significant role for both subclasses of IgG antibodies in this guinea pig model of TMA-induced occupational asthma.
偏苯三酸酐（TMA）是一种用于油漆和塑料工业的小分子化学物质，可导致人类出现类似哮喘的症状。经皮内注射TMA致敏的豚鼠会对抗原激发产生类似哮喘的症状，包括立即出现支气管收缩以及延迟性的肺部细胞浸润，尤其是嗜酸性粒细胞浸润。致敏豚鼠会产生TMA特异性IgG1，在该动物模型的哮喘反应中，这种抗体被认为很重要；然而，它们也会产生TMA特异性IgG2抗体。本研究的目的是确定IgG1和IgG2在TMA诱导的豚鼠即时支气管收缩和延迟性细胞浸润中的作用。通过气管内滴注TMA特异性IgG2、富含TMA特异性IgG1的抗体制剂或两者的组合，使豚鼠被动致敏。通过气管内滴注与豚鼠血清白蛋白结合的TMA（TMA-GPSA）来诱导过敏反应。与单独用IgG2或IgG1制剂致敏的动物相比，用IgG2和IgG1制剂组合致敏的动物观察到明显更强的支气管收缩反应。在抗原激发24小时后，通过支气管肺泡灌洗（BAL）细胞的差异细胞计数以及分别使用嗜酸性粒细胞过氧化物酶（EPO）和髓过氧化物酶（MPO）活性来量化细胞浸润，以分别衡量嗜酸性粒细胞和中性粒细胞的数量。在BAL中，单独用IgG2被动致敏会导致TMA诱导的MPO和EPO活性均增加。相比之下，在肺部，单独用部分纯化的TMA特异性IgG1制剂被动致敏会导致TMA诱导的EPO活性显著增加。与单独使用任何一种抗体制剂相比，用IgG2与IgG1制剂联合被动致敏会导致细胞浸润和肺损伤增强。这些数据表明，添加IgG2可增强IgG1介导的反应，并提示IgG抗体的两个亚类在这个TMA诱导的职业性哮喘豚鼠模型中都起着重要作用。
