title: Adiponectin attenuates human eosinophil adhesion and chemotaxis: implications in allergic inflammation.
abstract: OBJECTIVE
  Growing evidence has shown an association between obesity and asthma. Adiponectin, an adipocyte-derived cytokine, is known to have anti-inflammatory effects with reduced concentrations in obese subjects. Recent findings raised the intriguing possibility that adiponectin might play a role in allergic inflammation, although the mechanistic basis for their relationship remains unclear. The purpose of this study was to examine whether adiponectin might affect functions of eosinophils, which play an important role in the pathogenesis of asthma.
  
  
  METHODS
  Human peripheral blood eosinophils were purified to study expression of adiponectin receptors AdipoR1 and AdipoR2 using RT-PCR and flow cytometry. The effect of adiponectin on eosinophil survival was investigated using annexin V and propidium iodide staining. Eotaxin-induced cell adhesion was investigated using ICAM-1-coated plates. A Boyden chamber and real-time horizontal migration system were used for eotaxin-directed chemotaxis assay. Expression of eotaxin receptor CCR3 and intracellular calcium influx were assessed by flow cytometry.
  
  
  RESULTS
  AdipoR1 and AdipoR2 were expressed in human eosinophils. Adiponectin did not affect eosinophil survival or CCR3 expression; however, eotaxin-enhanced adhesion was inhibited by pretreatment with adiponectin. Adiponectin also diminished eotaxin-directed chemotactic responses by disturbing both velocity and directionality. Calcium influx in response to eotaxin was attenuated by adiponectin.
  
  
  CONCLUSIONS
  These results indicate that adiponectin attenuates the eosinophil functions induced by eotaxin without affecting cell viability. The inhibitory effect was associated with diminished calcium signaling rather than altering of surface receptor expression. Increasing circulating adiponectin might be a novel therapeutic modality for treatment of asthma, especially in obese asthmatics.
authors.affiliation: Department of Infection, Allergy, Clinical Immunology and Laboratory Medicine, Akita University Graduate School of Medicine , Akita , Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Yamamoto
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Ueki
authors.forename: Yuki
authors.initials: Y
authors.lastname: Moritoki
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Hajime
authors.initials: H
authors.lastname: Oyamada
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Konno
authors.forename: Mami
authors.initials: M
authors.lastname: Tamaki
authors.forename: Masamichi
authors.initials: M
authors.lastname: Itoga
authors.forename: Masahide
authors.initials: M
authors.lastname: Takeda
authors.forename: Wataru
authors.initials: W
authors.lastname: Ito
authors.forename: Junichi
authors.initials: J
authors.lastname: Chihara
mesh_terms: D052242:Adiponectin / Q000276:immunology*; D001249:Asthma / Q000276:immunology*; D020013:Calcium Signaling / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology*; D002470:Cell Survival / Q000276:immunology; D002633:Chemotaxis / Q000276:immunology*; D004804:Eosinophils / Q000166:cytology / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D009504:Neutrophils / Q000276:immunology; D012313:RNA / Q000737:chemistry / Q000235:genetics; D054419:Receptors, Adiponectin / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D052242:Adiponectin; D054419:Receptors, Adiponectin; D012313:RNA