title: IFN-γ-inducible protein of 10 kDa upregulates the effector functions of eosinophils through β2 integrin and CXCR3.
abstract: 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.
authors: Department of Respiratory Medicine, Saitama Medical University, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama, Japan.
authors: Yotaro
authors: Y
authors: Takaku
authors: Kazuyuki
authors: K
authors: Nakagome
authors: Takehito
authors: T
authors: Kobayashi
authors: Koichi
authors: K
authors: Hagiwara
authors: Minoru
authors: M
authors: Kanazawa
authors: Makoto
authors: M
authors: Nagata
mesh_terms: D000328:Adult; D018821:CD18 Antigens / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D054357:Chemokine CXCL10 / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D004804:Eosinophils / Q000378:metabolism*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D008024:Ligands; D008297:Male; D054367:Receptors, CXCR3 / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology*; D055815:Young Adult
chemical_list: D018821:CD18 Antigens; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D008024:Ligands; D054367:Receptors, CXCR3; D007371:Interferon-gamma