新型抗过敏药物哌罗昔康对人嗜酸性粒细胞白三烯C4及颗粒蛋白释放的抑制作用

Inhibitory effect of pemirolast, a novel antiallergic drug, on leukotriene C4 and granule protein release from human eosinophils.

作者信息

Kawashima T, Iwamoto I, Nakagawa N, Tomioka H, Yoshida S

机构信息

Research Laboratories, Tokyo Tanabe Co. Ltd., Japan.

出版信息

Int Arch Allergy Immunol. 1994;103(4):405-9. doi: 10.1159/000236662.

DOI:10.1159/000236662

PMID:8130655

Abstract

To determine whether pemirolast, a new antiallergic drug, inhibits the activation of eosinophils, we investigated the effect of pemirolast on the release of leukotriene C4 (LTC4) and eosinophil cationic protein (ECP) from human eosinophils. Calcium ionophore A23187 caused both LTC4 and ECP release from human eosinophils, whereas PAF and FMLP induced only ECP release from the eosinophils. Pemirolast (10(-6) to 10(-3) M) inhibited A23187-induced LTC4 release from the eosinophils in a dose-dependent fashion with 77% inhibition at 10(-3) M. Pemirolast (10(-5) to 10(-3) M) inhibited A23187-induced ECP release from the eosinophils in a dose-dependent fashion with 42% inhibition at 10(-3) M. Pemirolast (10(-4) and 10(-3) M) also inhibited PAF-induced and FMLP-induced ECP release from the eosinophils. We conclude that pemirolast prevents the activation of human eosinophils to inhibit LTC4 and ECP release. These results suggest that pemirolast might be useful in controlling allergic diseases by inhibiting eosinophil activation.

摘要

为了确定新型抗过敏药物吡嘧司特是否抑制嗜酸性粒细胞的活化，我们研究了吡嘧司特对人嗜酸性粒细胞白三烯C4（LTC4）和嗜酸性粒细胞阳离子蛋白（ECP）释放的影响。钙离子载体A23187可引起人嗜酸性粒细胞释放LTC4和ECP，而血小板活化因子（PAF）和N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸（FMLP）仅诱导嗜酸性粒细胞释放ECP。吡嘧司特（10⁻⁶至10⁻³M）以剂量依赖性方式抑制A23187诱导的嗜酸性粒细胞LTC4释放，在10⁻³M时抑制率为77%。吡嘧司特（10⁻⁵至10⁻³M）以剂量依赖性方式抑制A23187诱导的嗜酸性粒细胞ECP释放，在10⁻³M时抑制率为42%。吡嘧司特（10⁻⁴和10⁻³M）也抑制PAF诱导和FMLP诱导的嗜酸性粒细胞ECP释放。我们得出结论，吡嘧司特可阻止人嗜酸性粒细胞的活化，从而抑制LTC4和ECP释放。这些结果表明，吡嘧司特可能通过抑制嗜酸性粒细胞活化而有助于控制过敏性疾病。