Stevens W H, Inman M D, Wattie J, O'Byrne P M
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Am J Respir Crit Care Med. 1995 May;151(5):1526-31. doi: 10.1164/ajrccm.151.5.7735610.
Allergen inhalation causes airway hyperresponsiveness and airway inflammation in dogs. The purpose of this study was to determine whether allergen-induced airway hyperresponsiveness is associated with increases in oxygen radical production from bronchoalveolar lavage (BAL) cells. A group of 10 random-source dogs were studied twice, 4 wk apart. On each occasion, acetylcholine (ACh) airway responsiveness was measured before and 24 h after inhalation of Ascaris suum or its diluent, followed by BAL. The response to ACh was expressed as the concentration causing an increase in lung resistance of 5 cm H2/O/L/s above baseline. Spontaneous and phorbol myristate acetate (PMA)-stimulated (2.4 mumol/L) oxygen radical release were measured, for 10 min each, from washed BAL cells (4 x 10(6) cells/ml) by luminol-enhanced chemiluminescence in a luminometer at 37 degrees C. Superoxide anion production was measured using a cytochrome c assay. Allergen inhalation caused bronchoconstriction, airway inflammation, and airway hyperresponsiveness. The acetylcholine provocative concentration fell from 7.47 mg/ml (% SEM 1.61) before to 1.23 mg/ml (% SEM 1.62) after allergen (p < 0.0001). Allergen inhalation significantly increased absolute neutrophil (p = 0.03) and eosinophil (p = 0.02) counts in BAL. Spontaneous (p < 0.0003) and PMA-stimulated (p < 0.0005) chemiluminescence and superoxide anion production (p = 0.039) were increased after allergen inhalation. The allergen-induced increases in chemiluminescence were significantly correlated with the increases in ACh airway hyperresponsiveness (r = 0.75, p < 0.012). These results indicate that inhaled allergen increases oxygen radical release from bronchoalveolar lavage cells and supports the hypothesis that oxygen radicals are important in causing allergen-induced airway hyperresponsiveness.
吸入变应原可导致犬气道高反应性和气道炎症。本研究的目的是确定变应原诱导的气道高反应性是否与支气管肺泡灌洗（BAL）细胞产生氧自由基增加有关。一组10只随机来源的犬接受了两次研究，间隔4周。每次研究时，在吸入猪蛔虫或其稀释剂之前和之后24小时测量乙酰胆碱（ACh）气道反应性，随后进行支气管肺泡灌洗。对ACh的反应以导致肺阻力比基线增加5 cm H₂O/L/s的浓度表示。通过在37℃的发光计中使用鲁米诺增强化学发光法，对洗涤后的BAL细胞（4×10⁶个细胞/ml）分别测量10分钟的自发和佛波酯肉豆蔻酸酯（PMA）刺激（2.4 μmol/L）的氧自由基释放。使用细胞色素c测定法测量超氧阴离子的产生。吸入变应原导致支气管收缩、气道炎症和气道高反应性。变应原吸入后，乙酰胆碱激发浓度从之前的7.47 mg/ml（% SEM 1.61）降至1.23 mg/ml（% SEM 1.62）（p < 0.0001）。吸入变应原显著增加了BAL中绝对中性粒细胞（p = 0.03）和嗜酸性粒细胞（p = 0.02）计数。吸入变应原后，自发（p < 0.0003）和PMA刺激（p < 0.0005）的化学发光以及超氧阴离子产生（p = 0.039）均增加。变应原诱导的化学发光增加与ACh气道高反应性的增加显著相关（r = 0.75，p < 0.012）。这些结果表明，吸入变应原可增加支气管肺泡灌洗细胞的氧自由基释放，并支持氧自由基在引起变应原诱导的气道高反应性中起重要作用的假说。
