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IFN-γ-inducible protein of 10 kDa upregulates the effector functions of eosinophils through β(2 )integrin and CXCR3
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 incl...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3215664/ https://www.ncbi.nlm.nih.gov/pubmed/22004287 http://dx.doi.org/10.1186/1465-9921-12-138 |
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author | Takaku, Yotaro Nakagome, Kazuyuki Kobayashi, Takehito Hagiwara, Koichi Kanazawa, Minoru Nagata, Makoto |
author_facet | Takaku, Yotaro Nakagome, Kazuyuki Kobayashi, Takehito Hagiwara, Koichi Kanazawa, Minoru Nagata, Makoto |
author_sort | Takaku, Yotaro |
collection | PubMed |
description | 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 (O(2)(-)) 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 O(2)(- )generation in the presence of ICAM-1. Both the enhanced adhesion and O(2)(- )generation were inhibited by an anti-β(2 )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 O(2)(- )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. |
format | Online Article Text |
id | pubmed-3215664 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-32156642011-11-15 IFN-γ-inducible protein of 10 kDa upregulates the effector functions of eosinophils through β(2 )integrin and CXCR3 Takaku, Yotaro Nakagome, Kazuyuki Kobayashi, Takehito Hagiwara, Koichi Kanazawa, Minoru Nagata, Makoto Respir Res Research 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 (O(2)(-)) 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 O(2)(- )generation in the presence of ICAM-1. Both the enhanced adhesion and O(2)(- )generation were inhibited by an anti-β(2 )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 O(2)(- )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. BioMed Central 2011 2011-10-17 /pmc/articles/PMC3215664/ /pubmed/22004287 http://dx.doi.org/10.1186/1465-9921-12-138 Text en Copyright ©2011 Takaku et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Takaku, Yotaro Nakagome, Kazuyuki Kobayashi, Takehito Hagiwara, Koichi Kanazawa, Minoru Nagata, Makoto IFN-γ-inducible protein of 10 kDa upregulates the effector functions of eosinophils through β(2 )integrin and CXCR3 |
title | IFN-γ-inducible protein of 10 kDa upregulates the effector functions of eosinophils through β(2 )integrin and CXCR3 |
title_full | IFN-γ-inducible protein of 10 kDa upregulates the effector functions of eosinophils through β(2 )integrin and CXCR3 |
title_fullStr | IFN-γ-inducible protein of 10 kDa upregulates the effector functions of eosinophils through β(2 )integrin and CXCR3 |
title_full_unstemmed | IFN-γ-inducible protein of 10 kDa upregulates the effector functions of eosinophils through β(2 )integrin and CXCR3 |
title_short | IFN-γ-inducible protein of 10 kDa upregulates the effector functions of eosinophils through β(2 )integrin and CXCR3 |
title_sort | ifn-γ-inducible protein of 10 kda upregulates the effector functions of eosinophils through β(2 )integrin and cxcr3 |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3215664/ https://www.ncbi.nlm.nih.gov/pubmed/22004287 http://dx.doi.org/10.1186/1465-9921-12-138 |
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