Sagara H, Ra C, Okada T, Shinohara S, Fukuda T, Okumura K, Makino S
Department of Internal Medicine and Clinical Immunology, Dokkyo University, School of Medicine, Tochigi, Japan.
Int Arch Allergy Immunol. 1996;111 Suppl 1:32-6. doi: 10.1159/000237412.
Preferential eosinophil accumulation is characteristic of airway inflammation in asthma. Although little is known about its mechanism, the effect of a sialyl Lewis X analog on airway eosinophilia was examined in a guinea-pig model of asthma. Guinea-pigs were sensitized by repeated inhalation of ovalbumin. After a single inhalation challenge, the animals showed striking airway eosinophilia and a late asthmatic response. In contrast, when guinea-pigs were pretreated intravenously with sialyl Lewis X analog (LX 0104) 1 h before antigen challenge, both eosinophil infiltration in the tracheal wall and the late asthmatic response were significantly inhibited in a dose-dependent manner. In a further in vitro study, LX 0104 significantly suppressed the adhesion of human and guinea-pig eosinophils to human umbilical vein endothelial cells activated with interleukin-1 beta. These results suggest that LX 0104 plays a critical role in antigen-induced airway eosinophilia and the late asthmatic response.
嗜酸性粒细胞的优先积聚是哮喘气道炎症的特征。尽管对其机制了解甚少，但在豚鼠哮喘模型中研究了唾液酸化路易斯X类似物对气道嗜酸性粒细胞增多的影响。通过反复吸入卵清蛋白使豚鼠致敏。单次吸入激发后，动物表现出明显的气道嗜酸性粒细胞增多和迟发性哮喘反应。相比之下，当豚鼠在抗原激发前1小时静脉注射唾液酸化路易斯X类似物（LX 0104）时，气管壁中的嗜酸性粒细胞浸润和迟发性哮喘反应均以剂量依赖方式受到显著抑制。在进一步的体外研究中，LX 0104显著抑制人及豚鼠嗜酸性粒细胞与人脐静脉内皮细胞在白细胞介素-1β激活后的黏附。这些结果表明，LX 0104在抗原诱导的气道嗜酸性粒细胞增多和迟发性哮喘反应中起关键作用。
