β2-肾上腺素能激动剂对嗜酸性粒细胞黏附、超氧阴离子生成及脱颗粒的影响。

Effect of beta2-adrenergic agonists on eosinophil adhesion, superoxide anion generation, and degranulation.

作者信息

Noguchi Toru, Nakagome Kazuyuki, Kobayashi Takehito, Ueda Yutaka, Soma Tomoyuki, Nakamoto Hidetomo, Nagata Makoto

机构信息

Allergy Center, Saitama Medical University, Saitama, Japan; Department of Respiratory Medicine, Saitama Medical University, Saitama, Japan; Department of General Internal Medicine, Saitama Medical University, Saitama, Japan.

Allergy Center, Saitama Medical University, Saitama, Japan; Department of Respiratory Medicine, Saitama Medical University, Saitama, Japan.

出版信息

Allergol Int. 2015 Sep;64 Suppl:S46-53. doi: 10.1016/j.alit.2015.05.009. Epub 2015 Jul 5.

DOI:10.1016/j.alit.2015.05.009

PMID:26344080

Abstract

BACKGROUND

Eosinophils play important roles in the development of asthma exacerbation. Viral infection is a major cause of asthma exacerbation, and the expression of IFN-γ-inducible protein of 10 kDa (IP-10) and cysteinyl leukotrienes (cysLTs) is up-regulated in virus-induced asthma. As β2-adrenergic agonists, such as formoterol or salbutamol, are used to treat asthma exacerbation, we examined whether formoterol or salbutamol could modify eosinophil functions such as adhesiveness, particularly those activated by cysLTs or IP-10.

METHODS

Eosinophils were isolated from the blood of healthy subjects and were pre-incubated with either formoterol or salbutamol, and subsequently stimulated with IL-5, LTD4, or IP-10. Adhesion of eosinophils to intercellular cell adhesion molecule (ICAM)-1 was measured using eosinophil peroxidase assays. The generation of eosinophil superoxide anion (O2(-)) was examined based on the superoxide dismutase-inhibitable reduction of cytochrome C. Eosinophil-derived neurotoxin (EDN) release was evaluated by ELISA as a marker of degranulation.

RESULTS

Neither formoterol nor salbutamol suppressed the spontaneous adhesion of eosinophils to ICAM-1. However, when eosinophils were activated by IL-5, LTD4, or IP-10, formoterol, but not salbutamol, suppressed the adhesion to ICAM-1. Formoterol also suppressed IL-5, LTD4, or IP-10 induced eosinophil O2(-) generation or EDN release.

CONCLUSIONS

These findings suggest that formoterol, but not salbutamol, suppresses eosinophil functions enhanced by IL-5, LTD4, or IP-10. As these factors are involved in the development of asthma exacerbation, our results strongly support the hypothesis that administration of formoterol is a novel strategy for treating asthma exacerbation.

摘要

背景

嗜酸性粒细胞在哮喘急性加重的发生发展中起重要作用。病毒感染是哮喘急性加重的主要原因，在病毒诱导的哮喘中，10 kDa的γ干扰素诱导蛋白（IP-10）和半胱氨酰白三烯（cysLTs）的表达上调。由于β2肾上腺素能激动剂，如福莫特罗或沙丁胺醇，用于治疗哮喘急性加重，我们研究了福莫特罗或沙丁胺醇是否能改变嗜酸性粒细胞的功能，如黏附性，特别是那些由cysLTs或IP-10激活的功能。

方法

从健康受试者的血液中分离出嗜酸性粒细胞，先用福莫特罗或沙丁胺醇预孵育，随后用白细胞介素-5（IL-5）、白三烯D4（LTD4）或IP-10刺激。使用嗜酸性粒细胞过氧化物酶测定法测量嗜酸性粒细胞与细胞间黏附分子（ICAM）-1的黏附。基于超氧化物歧化酶抑制的细胞色素C还原来检测嗜酸性粒细胞超氧阴离子（O2(-)）的生成。通过酶联免疫吸附测定（ELISA）评估嗜酸性粒细胞衍生神经毒素（EDN）的释放，作为脱颗粒的标志物。