Kato M, Morikawa A, Kimura H, Shimizu T, Nakano M, Kuroume T
Department of Pediatrics, Gunma University School of Medicine, Japan.
Int Arch Allergy Appl Immunol. 1991;96(2):128-33. doi: 10.1159/000235483.
Airway inflammation with human polymorphonuclear leukocytes (PMNs) may play an important role in the pathophysiology of bronchial asthma. Superoxide anion (O2-) and other active oxygen species derived from PMNs cause tissue damage. To evaluate the effects of antiasthma drugs on airway inflammation or antioxidative actions due to the inhibition of O2- generation, we investigated the effects of antiallergic drugs, beta-adrenergic agonists, theophylline and corticosteroids, on the in vitro generation of O2- by human PMNs, using a chemiluminescence (CL) method dependent on a Cypridina luciferin analog (MCLA), a highly sensitive and specific CL probe for O2-. We found that azelastine, one of the antiallergic drugs, and isoproterenol inhibited FMLP-induced O2- generation in a dose-dependent fashion, whereas the other drugs exhibited no such inhibitory action except at very high concentrations. Furthermore, we found that isoproterenol inhibited O2- generation from the hypoxanthine-xanthine oxidase system (an O2(-)-generating system) in a dose-dependent fashion, unlike azelastine and the other drugs. These results suggest that azelastine and isoproterenol inhibit the process of O2- generation from PMNs, while isoproterenol also scavenges O2-. These drugs may be beneficial in the treatment of airway inflammation due to O2- generation in bronchial asthma.
人多形核白细胞（PMN）引发的气道炎症可能在支气管哮喘的病理生理学中起重要作用。PMN产生的超氧阴离子（O2-）和其他活性氧会导致组织损伤。为了评估抗哮喘药物对气道炎症的影响或因抑制O2-生成而产生的抗氧化作用，我们使用依赖于海萤荧光素类似物（MCLA）的化学发光（CL）方法，研究了抗过敏药物、β-肾上腺素能激动剂、茶碱和皮质类固醇对人PMN体外生成O2-的影响，MCLA是一种对O2-高度敏感且特异的CL探针。我们发现，抗过敏药物之一的氮卓斯汀和异丙肾上腺素以剂量依赖性方式抑制FMLP诱导的O2-生成，而其他药物除了在非常高的浓度下外没有这种抑制作用。此外，我们发现异丙肾上腺素以剂量依赖性方式抑制次黄嘌呤-黄嘌呤氧化酶系统（一个O2-生成系统）产生O2-，这与氮卓斯汀和其他药物不同。这些结果表明，氮卓斯汀和异丙肾上腺素抑制PMN产生O2-的过程，而异丙肾上腺素还能清除O2-。这些药物可能有助于治疗支气管哮喘中因O2-生成而导致的气道炎症。
