Department of Respiratory Medicine, Saitama Medical University, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama, Japan.
Respir Res. 2011 Oct 17;12(1):138. doi: 10.1186/1465-9921-12-138.
Eosinophils play an important role in the pathogenesis of bronchial asthma and its exacerbation. Recent reports suggest the involvement of IFN-γ-inducible protein of 10 kDa (IP-10) in virus-induced asthma exacerbation. The objective of this study was to examine whether CXCR3 ligands including IP-10 modify the effector functions of eosinophils.
Eosinophils isolated from the blood of healthy donors were stimulated with CXCR3 ligands and their adhesion to rh-ICAM-1 was then 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 to determine whether CXCR3 ligands induced eosinophil degranulation. Cytokine and chemokine production by eosinophils was examined using a Bio-plex assay.
Eosinophil adhesion to ICAM-1 was significantly enhanced by IP-10, which also significantly induced eosinophil O2- generation in the presence of ICAM-1. Both the enhanced adhesion and O2- generation were inhibited by an anti-β2 integrin mAb or an anti-CXCR3 mAb. Other CXCR3 ligands, such as monokine induced by IFN-γ (Mig) and IFN-inducible T cell α chemoattractant (I-TAC), also induced eosinophil adhesion and O2- generation in the presence of ICAM-1. IP-10, but not Mig or I-TAC, increased the release of EDN. IP-10 increased the production of a number of cytokines and chemokines by eosinophils.
These findings suggest that CXCR3 ligands such as IP-10 can directly upregulate the effector functions of eosinophils. These effects might be involved in the activation and infiltration of eosinophils in the airway of asthma, especially in virus-induced asthma exacerbation.
嗜酸性粒细胞在支气管哮喘及其恶化的发病机制中起着重要作用。最近的报告表明，γ-干扰素诱导蛋白 10kDa（IP-10）参与了病毒诱导的哮喘恶化。本研究的目的是检测包括 IP-10 在内的 CXCR3 配体是否能调节嗜酸性粒细胞的效应功能。
从健康供者的血液中分离嗜酸性粒细胞，用 CXCR3 配体刺激，然后用嗜酸性粒细胞过氧化物酶测定法测定其对 rh-ICAM-1 的粘附。根据超氧化物歧化酶抑制的细胞色素 C 还原，检测嗜酸性粒细胞超氧化物阴离子（O2-）的生成。通过嗜酸性粒细胞衍生的神经毒素（EDN）释放来评估 CXCR3 配体是否诱导嗜酸性粒细胞脱颗粒。使用 Bio-plex 测定法检测嗜酸性粒细胞产生的细胞因子和趋化因子。
IP-10 显著增强了嗜酸性粒细胞对 ICAM-1 的粘附，并且在存在 ICAM-1 的情况下，还显著诱导了嗜酸性粒细胞 O2-的生成。抗β2 整合素 mAb 或抗 CXCR3 mAb 抑制了增强的粘附和 O2-生成。其他 CXCR3 配体，如 IFN-γ 诱导的单核细胞趋化蛋白（Mig）和 IFN 诱导的 T 细胞α趋化因子（I-TAC），也在存在 ICAM-1 的情况下诱导了嗜酸性粒细胞的粘附和 O2-生成。IP-10 增加了 EDN 的释放，但 Mig 或 I-TAC 则没有。IP-10 增加了嗜酸性粒细胞产生的一些细胞因子和趋化因子。
这些发现表明，CXCR3 配体，如 IP-10，可以直接上调嗜酸性粒细胞的效应功能。这些作用可能涉及到哮喘气道中嗜酸性粒细胞的激活和浸润，特别是在病毒诱导的哮喘恶化中。
