Ishida K, Kelly L J, Thomson R J, Beattie L L, Schellenberg R R
University of British Columbia Pulmonary Research Laboratory, St. Paul's Hospital, Vancouver, Canada.
J Appl Physiol (1985). 1989 Sep;67(3):1133-9. doi: 10.1152/jappl.1989.67.3.1133.
To test the hypothesis that the development of airway hyperresponsiveness (AHR) lasting greater than or equal to 3 days after the last antigenic exposure required repeated mediator release, we compared dose-response changes in lung resistance (RL) to acetylcholine (ACh) in animals sensitized with 1% ovalbumin (OA), 4% Bordatella pertussis aerosol and subsequently challenged with 0.5% OA aerosol twice weekly for 4-6 wk vs. animals receiving saline aerosol instead of OA. Despite antihistamine pretreatment, each OA challenge produced cyanosis and inspiratory indrawing. Blood gas analysis in six guinea pigs revealed an immediate fall in arterial PO2 (PaO2) from 104.3 +/- 4.9 to 35.4 +/- 2.2 Torr after a 1-min exposure to aerosolized OA. ACh dose-response measurements of RL 3 days after the last OA challenge demonstrated a leftward shift and an increased magnitude of response. These differences were less marked at 7 days, and by 14 days after the last OA challenge, ACh dose-response curves were not different from those of control guinea pigs. Sensitization without repeated antigen challenge did not cause hyperresponsiveness. Morphometric analysis showed significantly increased numbers of eosinophils in the epithelium of airways in hyperresponsive guinea pigs, without neutrophil infiltration or alterations in epithelium and airway wall areas. We conclude that repeated antigenic challenge, but not sensitization alone, causes prolonged AHR in guinea pigs, which is associated with tissue eosinophilia.
即末次抗原暴露后持续大于或等于3天的气道高反应性（AHR）的发展需要反复释放介质，我们比较了用1%卵清蛋白（OA）、4%百日咳博德特氏菌气雾剂致敏，随后每周两次用0.5%OA气雾剂激发4 - 6周的动物与接受盐水气雾剂而非OA的动物，其肺阻力（RL）对乙酰胆碱（ACh）的剂量反应变化。尽管进行了抗组胺预处理，但每次OA激发都会导致发绀和吸气内陷。对六只豚鼠的血气分析显示，雾化吸入OA 1分钟后，动脉血氧分压（PaO2）立即从104.3±4.9 Torr降至35.4±2.2 Torr。末次OA激发3天后对RL进行的ACh剂量反应测量显示，反应曲线向左移位且反应幅度增加。这些差异在7天时不太明显，到末次OA激发14天后，ACh剂量反应曲线与对照豚鼠的曲线没有差异。未进行反复抗原激发的致敏不会导致高反应性。形态计量学分析显示，高反应性豚鼠气道上皮中的嗜酸性粒细胞数量显著增加，无中性粒细胞浸润，上皮和气道壁面积也无改变。我们得出结论，反复抗原激发而非仅致敏会导致豚鼠出现持续性AHR，这与组织嗜酸性粒细胞增多有关。
