Research to Elucidate the Underlying Mechanisms of Airway Hyperreactivity.

为了阐明支气管高反应性的潜在机制，我们采用了我们最初开发的几种动物模型以及正常人和哮喘和COPD患者。本研究的主要结果和结论如下：1）C型流感病毒感染可引起Beagle犬气道高反应性，尤其是感染后1 ~ 3周，支气管肺泡灌洗液（BALF）中ast细胞数量增加，组胺、TXB_2和PGF_（2 α）浓度升高。组织学研究还显示气道上皮细胞的损伤和脱落，这可能提示EDRF功能障碍。2）在以二氧化硅作为佐剂的致敏豚鼠中，猪蛔虫抗原吸入产生了较高的LAR（迟发性哮喘反应）发生率。在LAR处，在粘膜组织中观察到明显的嗜酸性粒细胞浸润。LAR可以通过选择性和COM的管理来阻止 ...更多信息 抗白三烯剂ONO-1078吸入超氧化物可引起猫气道收缩和气道高反应性，并可被超氧化物清除剂SOD阻断。在另一项研究中，SOD也减弱了吸入臭氧后气道反应性的增加。结果表明，超氧化物是产生气道高反应性的重要因素。4）在阻断交感神经和副交感神经后，吸入辣椒素或柠檬酸使猫和人受试者的狭窄气道扩张，这被神经节阻滞剂六甲铵（C6）阻断，结果表明，支气管C纤维受体和刺激性受体也是NAIS的受体，构成了反射通路。此外，刺激NAIS还能抑制速发型变态反应，显示对肺阻力增加和组胺浓度增加的保护作用。5）通过对猫气管粘膜下腺体的研究，观察了自主神经、P物质和VIP对收缩和分泌的影响。我们还发现上皮细胞产生一种抑制粘液分泌的物质。少

To elucidate the underlying mechanisms of bronchial hyperreactivity we have employed several sorts of animal models originally developed by us as well as normal subjects and patients with asthma and COPD. A summary of the results and conclusions which the research has attained to the present is as follows;1) ype C influenza virus infection induced airway hyperresponsiveness in Beagle dogs, especially 1 to 3 weeks after the infection, when an increase in the number of ast cells and concentrations of histamine, TXB2 and PGF2alpha in BALF were observed. Histological study also revealed damage and desquamation of the epithelial cells of the airways, which may suggest dysfunction of the EDRF.2) Ascaris suum antigen inhalation produced a higher incidence rate of LAR (late asthmatic response) in sensitized guinea pigs with silica as an adjuvant. At the LAR a distinct eosinophilic infiltration was observed in the mucosal tissue. The LAR can be blocked by administration of the selective and com … More petitive leukotriene blocker, ONO-1078. Airway hyperresponsiveness was also observed after the LAR, and was sustained for three to four day, which is possibly attributable to eosinophil infiltration.3) Superoxide inhalation produced airway contraction and subsequent airway hyperresponsiveness in cats, which was blocked by the administration of SOD, a scavenger of superoxide. In another study SOD also attenuated the increase in airway responsiveness after ozone inhalation. The results indicate that superoxide is an important factor in the production of hyperresponsiveness in the airway.4) After blocking sympathetic and parasympathetic nerves, inhalation of capsaicin or citric acid produced a dilatation of constricted airways in cats and human subjects, which was blocked by hexamethonium (C6), a ganglion blocker, The results indicate bronchial C-fiber receptors as well irritant receptors are also the receptors for the NAIS, which composes the reflex pathways. In addition, the stimulation of the NAIS also inhibited the immediate allergic reaction, revealing a protection against increase in lung resistance as well as histamine concentration.5) Through the study of single submucosal glands taken from cat trachea the effects of the autonomic nerves, substance-P, and VIP on contraction and secretion were determined. We also found that a substance is produced by epithelial cells which inhibits the mucous secretion. Less