Murine models of pulmonary diseases induced by adoptive transfer of T cell clones.

T 细胞克隆过继转移诱导的肺部疾病小鼠模型。

基本信息

批准号：
05807053
负责人：
YOKOYAMA Akihito
金额：
$ 1.22万
依托单位：
Ehime University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

项目摘要

We could not complete the experiments of above theme, because of some difficulties concerning maintenance of T cell clones. Instead, we report herein the results of fundamental experiments of the study. We have successfully made a murine model of antigen-driven pulmonary eosinophilia. Primed mice (BALB/c, 6-8wk old) with ovualbumin (OVA) and alum (three times, 2-wk interval) were challenged with OVA by inhalation (50mg/ml for 20min, 6 days) , yielded 9x10^5/ml Eo in bronchoalveolar lavage fluids (BALF) at 24-hours after the last challenge. Histological analysis revieled peribronchiolar and perivascular cell infiltration of lymphocytes and eosinophils. Recently, thromboxane A2 (TxA2) synthetase inhibitor (Sl) and receptor antagonist (RA) have been developed for the prophylaxis of bronchoconstriction. These compounds can improve pronchial hyperreactivity, indicating that the points of their action seem to be more than bronchoconstriction. To explore their influence on eosinophil (Eo) infiltration, we treated this model mice with OKY-046 (TxA2 Sl ; 100,10,1mg/kg) and S-1452 (TxA2 RA ; 25,2.5,0.25 mg/kg). Treatment with either compound significantly reduced Eo number in BALF in a dose-dependent manner up to-70% at the highest dose. Although we could detect IL-5 neither in BALF nor serum from untreated mice, the production of IL-5 decreased in culture supernatants of OVA plus spleen cells from treated mice with either compound in a dose-dependent manner up to-75% at the highest dose. The production of both interferon-gamma and IL-2 also significantly decreased. The cell differentials and percentages of CD3,4 or 8-positive splenocytes from treated mice were not significantly different from untreated mice. These results suggest that inhibition of TxA2 may reduce not only bronchoconstrictive response but also pulmonary infiltration of eosinophils by inhibiting cytokines production in vivo.

由于T细胞克隆的维持存在一些困难，我们无法完成上述主题的实验。相反，我们在此报告该研究的基本实验结果。我们已经成功制作了抗原驱动的肺嗜酸性粒细胞增多的小鼠模型。用卵白蛋白 (OVA) 和明矾（3 次，间隔 2 周）对小鼠（BALB/c，6-8 周龄）进行吸入 OVA 攻击（50mg/ml，20 分钟，6 天），产量为 9x10^5/最后一次攻击后 24 小时，支气管肺泡灌洗液 (BALF) 中含有 10ml Eo。组织学分析显示细支气管周围和血管周围有淋巴细胞和嗜酸性粒细胞浸润。最近，已经开发了血栓素A2(TxA2)合成酶抑制剂(S1)和受体拮抗剂(RA)用于预防支气管收缩。这些化合物可以改善支气管高反应性，表明它们的作用点似乎不仅仅是支气管收缩。为了探讨它们对嗜酸性粒细胞 (Eo) 浸润的影响，我们用 OKY-046 (TxA2 Sl ；100,10,1mg/kg) 和 S-1452 (TxA2 RA ；25,2.5,0.25 mg/kg) 治疗该模型小鼠。使用任一化合物治疗均以剂量依赖性方式显着降低 BALF 中的 Eo 数，最高剂量时可达 70%。虽然我们既不能在 BALF 中也不能在未处理小鼠的血清中检测到 IL-5，但在用任一化合物处理的小鼠的 OVA 加脾细胞的培养上清液中，IL-5 的产生以剂量依赖性方式减少了 75%。最高剂量。干扰素-γ 和 IL-2 的产生也显着减少。治疗小鼠的细胞差异和 CD3、4 或 8 阳性脾细胞百分比与未治疗小鼠没有显着差异。这些结果表明，抑制 TxA2 不仅可以减少支气管收缩反应，还可以通过抑制体内细胞因子的产生来减少嗜酸性粒细胞的肺部浸润。