Leach C L, Hatoum N S, Ratajczak H V, Zeiss C R, Garvin P J
IIT Research Institute, Veterans Administration Lakeside Medical Center, Chicago, IL 60616.
Am Rev Respir Dis. 1988 Jan;137(1):186-90. doi: 10.1164/ajrccm/137.1.186.
Trimellitic anhydride (TMA) is a chemical intermediate that has been shown to cause immunologically mediated respiratory syndromes in humans. We developed a rat model in which lung lesions accompanied by TMA-specific antibody resembled effects seen in humans. Two sets of experiments were undertaken to determine if TMA lung injury was primarily controlled by the immune system. Experiment 1: Rats were exposed to 95 micrograms/m3 of TMA 6 h/day, 5 days/wk for 2 wk during which time they received daily injections of either the immunosuppressant cyclophosphamide or saline. The TMA-exposed/saline control rats exhibited the usual TMA-induced lung lesions accompanied by TMA-specific antibody. However, the TMA-exposed/cyclophosphamide rats showed no lesions and no antibody. The spleen cells from all rats were subjected to lymphocyte blastogenesis assays using T- and B-cell mitogens. Results confirmed that cyclophosphamide-treated rats showed very little if any blastogenic response, whereas saline-treated rats gave the normal immune response. Thus, cyclophosphamide eliminated T- and B-cell function, which in turn prevented the occurrence of TMA lesions. Experiment 2: An initial passive transfer experiment showed that serum from TMA-sensitized rats could be adoptively transferred into naive recipient rats, which when given a single TMA inhalation challenge exhibited TMA-induced lesions. Similar attempts to transfer spleen cells or spleen cells plus serum did not predispose recipients for lesions. A second modified passive transfer of sensitized serum using a larger number of recipient rats, followed by a TMA challenge, resulted in lesions in 14 of the 16 rats.(ABSTRACT TRUNCATED AT 250 WORDS)
偏苯三酸酐（TMA）是一种化学中间体，已被证明可导致人类免疫介导的呼吸系统综合征。我们建立了一种大鼠模型，其中伴有TMA特异性抗体的肺部病变类似于在人类身上看到的效应。进行了两组实验以确定TMA肺损伤是否主要由免疫系统控制。实验1：大鼠每天6小时、每周5天暴露于95微克/立方米的TMA中，持续2周，在此期间它们每天接受免疫抑制剂环磷酰胺或生理盐水注射。暴露于TMA/生理盐水对照组的大鼠表现出常见的TMA诱导的肺部病变，并伴有TMA特异性抗体。然而，暴露于TMA/环磷酰胺的大鼠没有出现病变，也没有抗体。使用T细胞和B细胞有丝分裂原对所有大鼠的脾细胞进行淋巴细胞增殖试验。结果证实，环磷酰胺处理的大鼠即使有任何增殖反应也非常少，而生理盐水处理的大鼠则有正常的免疫反应。因此，环磷酰胺消除了T细胞和B细胞功能，进而阻止了TMA病变的发生。实验2：最初的被动转移实验表明，来自TMA致敏大鼠的血清可以过继转移到未致敏的受体大鼠中，这些受体大鼠在单次吸入TMA激发后表现出TMA诱导的病变。类似的转移脾细胞或脾细胞加血清的尝试并没有使受体易患病变。使用更多受体大鼠进行的第二次改良的致敏血清被动转移，随后进行TMA激发，导致16只大鼠中的14只出现病变。（摘要截短于250字）
