Nagase T, Fukuchi Y, Matsuse T, Sudo E, Matsui H, Orimo H
Department of Geriatrics, Faculty of Medicine, University of Tokyo, Japan.
Am J Respir Crit Care Med. 1995 Apr;151(4):1244-9. doi: 10.1164/ajrccm/151.4.1244.
Airway inflammation is involved in the pathogenesis of bronchial asthma. Intercellular adhesion molecule-1 (ICAM-1) is a ligand for lymphocyte function-associated antigen-1 alpha (LFA-1 alpha) and has been shown to be required for leukocyte migration into inflamed area. The purpose of this report was to investigate the role of ICAM-1/LFA-1 alpha pathway in a rat model of extrinsic asthma using monoclonal antibodies (mAbs). We chose to study ovalbumin (OA)-sensitized Brown-Norway rats, an animal model in which there is a high prevalence of both early (ER) and late responses (LR) after antigen challenge. We measured tracheal and alveolar pressure using alveolar capsules in open-chested, mechanically ventilated animals to calculate resistance of lung (RL), tissue (Rti), and airway (Raw). In the OA group, both ER (RL, Rti, Raw = 263 +/- 16, 235 +/- 10, 309 +/- 38% baseline) and LR (RL, Rti, Raw = 265 +/- 26, 238 +/- 13, 316 +/- 55% baseline) were observed. The administration of mAbs to ICAM-1 and LFA-1 alpha significantly attenuated the ER (RL, Rti, Raw = 146 +/- 9, 141 +/- 11, 156 +/- 8% baseline) and LR (RL, Rti, Raw = 128 +/- 8, 124 +/- 5, 137 +/- 1% baseline), indicating that both airway and lung tissues were involved in this mechanism. The current observations suggest that ICAM-1/LFA-1 alpha pathway is involved in both the early and late responses in a rat model of allergic asthma. The antagonism of ICAM-1 and LFA-1 alpha may provide a potential therapeutic approach to the early and late responses of bronchial asthma.
气道炎症参与支气管哮喘的发病机制。细胞间黏附分子-1（ICAM-1）是淋巴细胞功能相关抗原-1α（LFA-1α）的配体，已被证明是白细胞迁移到炎症区域所必需的。本报告的目的是使用单克隆抗体（mAb）研究ICAM-1/LFA-1α通路在大鼠外源性哮喘模型中的作用。我们选择研究卵清蛋白（OA）致敏的Brown-Norway大鼠，这是一种在抗原激发后早期反应（ER）和晚期反应（LR）发生率都很高的动物模型。我们在开胸、机械通气的动物中使用肺泡囊测量气管和肺泡压力，以计算肺阻力（RL）、组织阻力（Rti）和气道阻力（Raw）。在OA组中，观察到了早期反应（RL、Rti、Raw = 263±16、235±10、309±38%基线）和晚期反应（RL、Rti、Raw = 265±26、238±13、316±55%基线）。给予针对ICAM-1和LFA-1α的单克隆抗体显著减轻了早期反应（RL、Rti、Raw = 146±9、141±11、156±8%基线）和晚期反应（RL、Rti、Raw = 128±8、124±5、137±1%基线），表明气道和肺组织都参与了这一机制。目前的观察结果表明，ICAM-1/LFA-1α通路参与了过敏性哮喘大鼠模型的早期和晚期反应。ICAM-1和LFA-1α的拮抗作用可能为支气管哮喘的早期和晚期反应提供一种潜在的治疗方法。
