Folkerts G, Henricks P A, Slootweg P J, Nijkamp F P
Department of Pharmacology, State University of Utrecht, The Netherlands.
Am Rev Respir Dis. 1988 Jun;137(6):1441-8. doi: 10.1164/ajrccm/137.6.1441.
It was investigated whether an endotoxin-induced airway inflammation and injury correlated with the induction of bronchial hyperreactivity. Guinea pigs were treated with an endotoxin aerosol, and 4 and 24 h later lung lavages were performed and a differential cell count was made. The number of neutrophils and monocytes was significantly increased (p less than 0.005) at these times. After 24 h, the number of eosinophils and lymphocytes was also increased (p less than 0.005). The number of alveolar macrophages remained unchanged. Histologic examination revealed increased intraluminal mucus and an influx of erythrocytes and neutrophils in the tracheal and bronchial lumen at both time points after the endotoxin aerosol. The epithelium was morphologically changed and contained many neutrophils. Focal matting and/or loss of cilia also occurred. Airway smooth muscle responsiveness was measured in vitro on isolated guinea pig tracheal smooth muscle preparations 4 and 24 h after endotoxin aerosol. No differences in the maximal responses or slope factors of the dose-response curves for carbachol, histamine, or isoprenaline were detected between the control and endotoxin-exposed groups. The EC50 value of the histamine dose-response curve 4 h after endotoxin nebulization was slightly but significantly (p less than 0.05) increased, indicating decreased sensitivity. Responsiveness in vivo was measured in anesthetized spontaneously breathing guinea pigs 24 h after the endotoxin aerosol. The histamine-induced increase in pulmonary resistance was reduced by about 35% in the endotoxin-nebulized group (p less than 0.01). It can be concluded that an influx of inflammatory cells accompanied by injury of the airways induces hyporeactivity of the guinea pig respiratory tract.
研究了内毒素诱导的气道炎症和损伤是否与支气管高反应性的诱导相关。用内毒素气雾剂处理豚鼠，4小时和24小时后进行肺灌洗并进行细胞分类计数。此时中性粒细胞和单核细胞的数量显著增加（p<0.005）。24小时后，嗜酸性粒细胞和淋巴细胞的数量也增加（p<0.005）。肺泡巨噬细胞的数量保持不变。组织学检查显示，在内毒素气雾剂处理后的两个时间点，气管和支气管腔内的管腔内黏液增加，红细胞和中性粒细胞流入。上皮细胞形态发生改变，含有许多中性粒细胞。还发生了局灶性纤毛缠结和/或纤毛缺失。在内毒素气雾剂处理4小时和24小时后，在离体豚鼠气管平滑肌制剂上体外测量气道平滑肌反应性。在对照组和内毒素暴露组之间，未检测到卡巴胆碱、组胺或异丙肾上腺素剂量反应曲线的最大反应或斜率因子有差异。内毒素雾化4小时后组胺剂量反应曲线的EC50值略有但显著增加（p<0.05），表明敏感性降低。在内毒素气雾剂处理24小时后，在麻醉的自主呼吸豚鼠体内测量反应性。在内毒素雾化组中，组胺诱导的肺阻力增加降低了约35%（p<0.01）。可以得出结论，炎症细胞的流入伴随着气道损伤会导致豚鼠呼吸道反应性降低。
