Wegner C D, Rothlein R, Gundel R H
Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877.
Agents Actions Suppl. 1991;34:529-44.
Using a primate antigen inhalation model the mechanisms involved in the induction of airway hyperresponsiveness were studied. Antigen inhalation induced a prolonged airway eosinophilia. Chronic airway eosinophilia, intratracheal instillation of eosinophil major basic protein, repeated antigen inhalation, and airway epithelial desquamation induced, or were associated with, an increase in airway responsiveness. Using monoclonal antibodies to intercellular adhesion molecule-1 (ICAM-1) and endothelial-leukocyte adhesion molecule-1 (ELAM-1), the contributions of these cell adhesion molecules to antigen-induced airway hyperresponsiveness were studied. ICAM-1 partially mediated eosinophil adhesion to endothelium in vitro, was upregulated on inflamed endothelium and epithelium in vitro and in vivo, and contributed to repeated antigen-induced airway eosinophilia and hyperresponsiveness. ELAM-1 was upregulated on inflamed endothelium (but not epithelium) in vitro and in vivo, but did not contribute to the repeated antigen-induced airway eosinophilia and hyperresponsiveness. These results indicate that antagonism of ICAM-1, but not ELAM-1, may provide a novel therapeutic approach to reducing the airway inflammation and hyperresponsiveness commonly found in asthmatics.
利用灵长类动物抗原吸入模型，对气道高反应性诱导过程中涉及的机制进行了研究。抗原吸入可导致气道嗜酸性粒细胞增多持续较长时间。慢性气道嗜酸性粒细胞增多、气管内滴注嗜酸性粒细胞主要碱性蛋白、反复抗原吸入以及气道上皮剥脱可诱导或与气道反应性增加相关。使用针对细胞间黏附分子-1（ICAM-1）和内皮细胞-白细胞黏附分子-1（ELAM-1）的单克隆抗体，研究了这些细胞黏附分子对抗原诱导的气道高反应性的作用。ICAM-1在体外可部分介导嗜酸性粒细胞与内皮的黏附，在体外和体内炎症的内皮和上皮细胞上均上调，并参与反复抗原诱导的气道嗜酸性粒细胞增多和高反应性。ELAM-1在体外和体内炎症的内皮细胞（而非上皮细胞）上上调，但不参与反复抗原诱导的气道嗜酸性粒细胞增多和高反应性。这些结果表明，拮抗ICAM-1而非ELAM-1可能为减轻哮喘患者常见的气道炎症和高反应性提供一种新的治疗方法。
