Contribution of anaphylatoxin C5a to late airway responses after repeated exposure of antigen to allergic rats
Contribution of anaphylatoxin C5a to late airway responses after repeated exposure of antigen to allergic rats
复制标题
DOI：
10.4049/jimmunol.167.8.4651
复制
发表时间：
2001-10-15
影响因子：
4.4
通讯作者：
Okada, H
中科院分区：
文献类型：
--
作者：
Abe, M;Shibata, K;Okada, H
我们试图阐明补体在过敏性哮喘中的作用。致敏的大鼠接受反复intrichheal暴露于OVA连续3天，肺阻力，然后估计最后一次曝光后6小时。而立即气道反应（IAR）的R-L往往减少的OVA暴露的数量成比例，晚期气道反应（LAR）成为突出后，三个。虽然术前用药与两种补体抑制剂，可溶性补体受体1型（sCR 1）或萘莫司他甲磺酸盐，导致抑制IAR后，无论是一个或两个曝光，LAR抑制后的三倍。在每次暴露于OVA之前预先给药C5 a受体拮抗剂（C5 aRA）也抑制了三次后的LAR。反复的OVA暴露导致嗜酸性粒细胞和中性粒细胞浸润到支气管粘膜下层，这被sCR 1或C5 aRA的前驱用药抑制。三次OVA暴露后，肺组织C5 aR mRNA表达上调，但C3 aR几乎没有上调。用sCR 1或C5 aRA预处理抑制肺中C5 aR表达的上调以及细胞因子信息。sCR 1预处理对LAR的抑制作用可被C5 aRA抑制的C5 a desArg逆转。与此相反，大鼠C3 a desArg或姜黄素诱导的中性粒细胞趋化因子-1诱导细胞浸润到支气管粘膜下层与OVA的共刺激，但这些都没有影响LAR。这些差异可能是由这样的事实，即共刺激与OVA和C5 a协同增强IAR，而与OVA和C3 a或姜黄素诱导的中性粒细胞趋化因子-1没有。由Ag-Ab复合物产生的C5 a有助于细胞因子的产生，并有助于反复暴露于Ag后的LAR。
We attempted to elucidate the contribution of complement to allergic asthma. Rat sensitized to OVA received repeated intratracheal exposures to OVA for up to 3 consecutive days, and pulmonary resistance was then estimated for up to 6 h after the last exposure. Whereas the immediate airway response (IAR) in terms of R-L tended to decrease in proportion to the number of OVA exposures, late airway response (LAR) became prominent only after three. Although premedication with two kinds of complement inhibitors, soluble complement receptor type 1 (sCR1) or nafamostat mesylate, resulted in inhibition of the IAR after either a single or a double exposure, the LAR was inhibited after the triple. Premedication with a C5a receptor antagonist (C5aRA) before every exposure to OVA also inhibited the LAR after three. Repeated OVA exposure resulted in eosinophil and neutrophil infiltration into the bronchial submucosa which was suppressed by premedication with sCR1 or C5aRA. Up-regulation of C5aR mRNA was shown in lungs after triple OVA exposure, but almost no up-regulation of C3aR. Pretreatment with sCR1 or C5aRA suppressed the up-regulation of C5aR expression as well as cytokine messages in the lungs. The suppression of LAR by pretreatment with sCR1 was reversed by intratracheal instillation of rat C5a desArg the action of which was inhibited by C5aRA. In contrast, rat C3a desArg or cytokine-induced neutrophil chemoattractant-1 induced cellular infiltration into the bronchial submucosa by costimulation with OVA, but these had no influence on the LAR. These differences might be explained by the fact that costimulation with OVA and C5a synergistically potentiated IAR, whereas that with OVA and either C3a or cytokine-induced neutrophil chemoattractant-1 did not. C5a generated by Ag-Ab complexes helps in the production of cytokines and contributes to the LAR after repeated exposure to Ag.