Tasic Tihana, Stephan Michael, von Hörsten Stephan, Pabst Reinhard, Schmiedl Andreas
Institute of Functional and Applied Anatomy, Hannover Medical School, Germany.
Clinic for Psychosomatics and Psychotherapy, Hannover Medical School, Germany.
Immunobiology. 2014 Nov;219(11):888-900. doi: 10.1016/j.imbio.2014.07.007. Epub 2014 Jul 22.
Many disease models have shown that, within the species rat, different strains are differentially susceptible to asthma-induced inflammation depending on the genetic background. Likewise, CD26/DPPIV-deficiency in asthmatic F344 rats has been shown to result in a less pronounced inflammation and in increased Treg cell influx into the lung compared to wild-types. The aim of the present study was to investigate whether the genetic background of the animals interferes with CD26/DPPIV-deficiency in a model of allergic-like inflammation, or whether the deficiency per se is the predominant regulator of the inflammation. Therefore, we hypothesised that CD26/DPPIV-deficient Dark Agouti (DA) rats also exhibit a less pronounced ovalbumin (OVA)-induced inflammation compared to wild-types. After sensitisation with OVA, Al(OH)3 and heat-killed Bordetella pertussis bacilli, animals were challenged three times with 5% aerosolized OVA at intervals of 24h, i.e., on three consecutive days. 24h after the third challenge, animals were sacrificed and examined. In both wild-type and CD26/DPPIV-deficient rat groups, asthma induction led to (1) lung inflammation, (2) significantly increased eosinophil infiltration in the BALF, (3) significantly increased IgE serum levels, (4) a significant increase of inflammatory cytokines, (5) a significant increase of different T cell populations in the lungs and in their draining lymph nodes, as well as to (6) a significantly higher number of all T lymphocyte subtypes in the blood. Thus, the degree of the OVA-induced Th2-driven pulmonary inflammation was similarly pronounced in both wild-type and CD26/DPPIV-deficient DA rats.
许多疾病模型表明，在大鼠物种中，不同品系因遗传背景不同，对哮喘诱导的炎症易感性也存在差异。同样，与野生型相比，哮喘F344大鼠的CD26/DPPIV缺陷已被证明会导致炎症减轻，且肺中调节性T细胞（Treg）流入增加。本研究的目的是调查在类过敏性炎症模型中，动物的遗传背景是否会干扰CD26/DPPIV缺陷，或者缺陷本身是否是炎症的主要调节因素。因此，我们假设与野生型相比，CD26/DPPIV缺陷的黑褐大鼠对卵清蛋白（OVA）诱导的炎症也表现出较轻的症状。用OVA、氢氧化铝（Al(OH)3）和热灭活的百日咳博德特氏杆菌致敏动物后，每隔24小时用5%雾化OVA对动物进行三次激发，即连续三天。第三次激发后24小时，处死动物并进行检查。在野生型和CD26/DPPIV缺陷大鼠组中，哮喘诱导均导致：（1）肺部炎症；（2）支气管肺泡灌洗液（BALF）中嗜酸性粒细胞浸润显著增加；（3）血清IgE水平显著升高；（4）炎性细胞因子显著增加；（5）肺及其引流淋巴结中不同T细胞群体显著增加；以及（6）血液中所有T淋巴细胞亚群数量显著增加。因此，OVA诱导的Th2驱动的肺部炎症程度在野生型和CD26/DPPIV缺陷的DA大鼠中同样明显。
