Differential effects of cyclosporine A after acute antigen challenge in sensitized cats in vivo and ex vivo.
Differential effects of cyclosporine A after acute antigen challenge in sensitized cats in vivo and ex vivo.
复制标题
环孢素 A 对致敏猫体内和离体急性抗原攻击后的不同作用。
DOI：
10.1038/sj.bjp.0701716
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发表时间：
1998
影响因子：
7.3
通讯作者：
Padrid,PA
中科院分区：
文献类型：
--
作者：
Mitchell,RW;Cozzi,P;Ndukwu,IM;Spaethe,S;Leff,AR;Padrid,PA
1我们确定了环孢素 A (CsA) 治疗对致敏猫体内肥大细胞脱颗粒和肺阻力 (RL) 以及抗原攻击后体外气管平滑肌 (TSM) 收缩的影响。我们还确定了在组织浴中添加 CsA 对 TSMin 体外抗原诱导反应的直接影响。2 只猫 (n=10) 通过肌肉注射致敏。注射蛔虫suumantigen (AA)； 5 只猫 (CsA+) 在急性抗原攻击前每天两次接受 CsA，持续 2 周，剂量足以抑制离体猫外周血单核细胞分泌白介素-2。3 暴露于 AA 10 分钟内，肺阻力相对增加 (P<0.03)。两组支气管肺泡灌洗液中的组胺含量在抗原攻击后 30 分钟内相对增加，CsA+ 从不可检测水平增至 AA 后 542±74 pg ml−1，从基线时的 74±19 pg ml−1 增至 AA 后 970±180 pg ml−1 CsA− （P<0.05；P=NS vs CsA+）。4在切除的 TSM 中，CsA+ 组中体外暴露于 AA 引起的主动张力为 107±38% KCl，而 CsA− 组中为 144±56% KCl (P=NS)。然而，当组织在体外与 1 μMCsA 预孵育时，两组收获的 TSM (n=4) 的收缩在 AA 攻击后被消除或大大减弱（8±8% KCl，P<0.05 与 CsA+ 和 CsA− 相比）。这与仅在体外用 CsA 处理的组织的器官浴液中 5-羟色胺的抑制释放有关。5我们证明，体内 CsA 治疗不会抑制过敏猫抗原攻击后的早期哮喘反应或肥大细胞脱颗粒。此外，CsA对肥大细胞功能的体外影响并不反映在特应性哮喘动物模型中CsA对体内肥大细胞功能缺乏影响。British Journal of Pharmacology(1998)123, 1198–1204; doi:10.1038/sj.bjp.0701716
1We determined the effect of cyclosporine A (CsA) treatment on mast cell degranulation and lung resistance (RL)in vivo, and tracheal smooth muscle (TSM) contractionex vivoafter antigen challenge in sensitized cats. We also determined the direct effects of addition of CsA to the tissue bath on antigen‐induced responses of TSMin vitro.2Cats (n=10) were sensitized by i.m. injection ofAscaris suumantigen (AA); 5 cats (CsA+) received CsA twice daily for 2 weeks before acute antigen challenge in doses sufficient to suppress interleukin‐2 secretion from feline peripheral blood mononuclear cellsex vivo.3Lung resistance increased comparably within 10 min of exposure to AA (P<0.03). Histamine content in bronchoalveolar lavage fluid from both groups increased comparably within 30 min of antigen challenge, from undetectable levels to 542±74 pg ml−1post AA for CsA+ and from 74±19 pg ml−1at baseline, to 970±180 pg ml−1post AA CsA− (P<0.05;P=NS vs CsA+).4In excised TSM, active tension elicited by exposure to AAin vitrowas 107±38% KCl in the CsA+ group vs 144±56% KCl in the CsA− group (P=NS). However, contraction of TSM (n=4) harvested from both groups was abolished or greatly diminished after AA challenge when tissues were pre‐incubated with 1 μMCsAin vitro(8±8% KCl,P<0.05 vs CsA+ and CsA−). This was associated with inhibited release of 5‐hydroxytryptamine into the organ bath fluid of tissues treated with CsAin vitroonly.5We demonstrated that CsA treatmentin vivodoes not inhibit the early phase asthmatic response or mast cell degranulation following antigen challenge in sensitized cats. Additionally, the effects of CsA on mast cell functionex vivodo not reflect lack of effects of CsA on mast cell functionin vivoin this animal model of atopic asthma.British Journal of Pharmacology(1998)123, 1198–1204; doi:10.1038/sj.bjp.0701716