Airway hyperreactivity elicited by toluene diisocyanate (TDI)-albumin conjugate is not accompanied by airway eosinophilic infiltration in guinea pigs
Airway hyperreactivity elicited by toluene diisocyanate (TDI)-albumin conjugate is not accompanied by airway eosinophilic infiltration in guinea pigs
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DOI：
10.1007/s002040050480
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发表时间：
1998-02-01
影响因子：
6.1
通讯作者：
Fedan, JS
中科院分区：
文献类型：
--
作者：
Huang, J;Millecchia, LL;Fedan, JS
甲苯二异氰酸酯(TDI)诱导的哮喘患者存在非特异性气道高反应性，然而，这种高反应性的潜在病理生理机制仍存在争议。在本研究中，我们使用了一种豚鼠模型来研究TDI诱导的气道高反应性与嗜酸性气道渗出的关系，这被广泛认为在过敏原诱导的高反应性的发展中起着关键作用。豚鼠经皮下注射致敏。第1天和第6天分别注射10亩L TDI。对照组注射生理盐水。第2次注射后2周，用TDI-GSA(豚鼠血清白蛋白)结合物测定吸入前和吸入后多次的气道反应性和比气道阻力(sr(Aw))。用酶组织化学法检测呼吸道中的嗜酸性粒细胞，并用计算机辅助图像分析进行定量。在TDI致敏动物的血液中发现了TDI特异性Ig G(1)抗体。TDI-GSA刺激后即刻，这些动物的sr(Aw)增加，并在TDI-GSA刺激后6h和18h观察到对乙酰胆碱的高反应性。然而，与对照动物相比，TDI-GSA挑战并没有导致呼吸道中嗜酸粒细胞的增加。结果提示，TDI诱导的气道高反应性的发生不依赖于嗜酸性粒细胞在气道的浸润。
Nonspecific airway hyperresponsiveness is present in many patients with toluene diisocyanate (TDI)-induced asthma; however, the underlying pathophysiological mechanisms of this hyperresponsiveness remain controversial. In the present study, we used a guinea pig model to investigate the association of TDI-induced airway hyperresponsiveness with eosinophilic airway infiltration, which is widely considered to play a key role in the development of allergen-induced hyperresponsiveness. Guinea pigs were sensitized by i.d. injections of 10 mu l TDI on day 1 and day 6. Control animals received saline injections. Two weeks after the second injection, airway reactivity to inhaled methacholine and specific airway resistance (sR(aw)) was measured before and at several times after inhalation challenge with TDI-GSA (guinea pig serum albumin) conjugates. Eosinophils in the airways were detected using enzyme histochemistry and quantified using computer-assisted image analysis. TDI-specific IgG(1) antibodies were found in the blood of TDI-sensitized animals. An immediate increase in sR(aw) was induced in these animals by TDI-GSA challenge; airway hyperresponsiveness to methacholine was observed at 6 h and 18 h after TDI-GSA challenge. However, TDI-GSA challenge did not result in an elevation of eosinophils in the airways, compared with control animals. The results suggest that the development of TDI-induced airway hyperresponsiveness is not dependent upon eosinophil infiltration in airways.