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首页> 外文期刊>Journal of applied toxicology >Strain differences influence timing and magnitude of both acute and late inflammatory reactions after intratracheal instillation of an alkylating agent in rats
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Strain differences influence timing and magnitude of both acute and late inflammatory reactions after intratracheal instillation of an alkylating agent in rats

机译：气管内滴注烷基化剂后，应变差异影响急性和晚期炎症反应的时间和大小

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The acute pulmonary responses after exposure to sulfur and nitrogen mustards are well documented whereas the late pulmonary effects are not. With a novel focus on the immune system this paper investigate whether late phase pulmonary effects developed in rats exposed to the nitrogen mustard melphalan are linked to the acute responses and whether the reactions are genetically regulated. The DA rat strain was used to establish a lung exposure model. Five other inbred rat strains (PVG, PVG.1AV1, LEW, WF and F344) were compared within the model at selected time points. All rat strains displayed a biphasic pattern of leukocyte infiltration in the lungs, dominated by neutrophils 2days after exposure and a second peak dominated by macrophages 29days after exposure. The number of macrophages was higher in the DA rat compared with the other strains. The infiltration of lymphocytes in the lungs varied in both time of appearance and magnitude between strains. The quantity of collagen deposition in the lungs varied between strains at day 90; LEW and WF displayed high collagen content which coincided with an increased level of cytotoxic T cells. LEW further displayed an increased number of T helper cells and natural killer (NK) T cells in the lungs. The results in this study suggest there is a link between the development of lung fibrosis and high cytotoxic cell responses and that there is a genetic influence, as there are variations in acute and late adverse reactions between rat strains in both timing and magnitude.
机译：充分证明了暴露于硫和氮芥末后的急性肺反应，而晚期肺反应则没有。本文以免疫系统为研究重点，探讨了暴露于芥菜氮芥对大鼠产生的晚期肺部影响是否与急性反应有关，以及这些反应是否受到基因调控。 DA大鼠品系用于建立肺暴露模型。在选定的时间点，在模型中比较了其他五种自交大鼠品系（PVG，PVG.1AV1，LEW，WF和F344）。所有大鼠品系均显示出双相型肺部白细胞浸润模式，在暴露后2天以嗜中性粒细胞为主，在暴露后29天以巨噬细胞为主的第二高峰。与其他品系相比，DA大鼠的巨噬细胞数量更高。肺部淋巴细胞的浸润在出现时间和菌株之间的大小上都不同。在第90天时，不同菌株之间肺中胶原蛋白沉积的量有所不同。 LEW和WF显示出高胶原含量，这与细胞毒性T细胞水平升高相吻合。 LEW还显示出肺中T辅助细胞和自然杀伤（NK）T细胞数量增加。这项研究的结果表明，肺纤维化的发展与高细胞毒性细胞反应之间存在联系，并且存在遗传影响，因为大鼠品系之间的急性和晚期不良反应在时间和强度上都有差异。

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