IFN-γ-inducible protein of 10 kDa upregulates the effector functions of eosinophils through β2 integrin and CXCR3

Respiratory Research

Makoto Nagata¹  Minoru Kanazawa²  Koichi Hagiwara²  Takehito Kobayashi¹  Kazuyuki Nakagome¹  Yotaro Takaku¹ 

[1]Allergy Center, Saitama Medical University, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama, Japan

[2]Department of Respiratory Medicine, Saitama Medical University, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama, Japan

关键词: rhinovirus;    IP-10;    ICAM-1;    acute exacerbation;    asthma;   

Others  :  796784
DOI  :  10.1186/1465-9921-12-138

 received in 2011-07-10, accepted in 2011-10-17,  发布年份 2011

【 摘 要 】

Background

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.

Methods

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.

Results

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.

Conclusions

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.

【 授权许可】

   
2011 Takaku et al; licensee BioMed Central Ltd.

【 图 表 】

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