title: Signaling through the beta2 integrin prolongs eosinophil survival.
abstract: BACKGROUND
  Recently, adhesion molecules have been suggested to play an important role in allergic inflammatory diseases such as bronchial asthma. It is unclear whether eosinophil activation and paracrine or autocrine synthesis of eosinophilopoietic growth cytokines is mediated through signaling by intercellular adhesion molecule-1 (ICAM-1) and the beta2 integrin family.
  
  
  OBJECTIVE
  We examined whether signaling by ICAM-1 and its ligands (beta2 integrins) could prolong eosinophil survival.
  
  
  METHODS
  Eosinophils were isolated from patients with hypereosinophilia by modified CD16 negative selection. After culture with or without recombinant soluble ICAM-1, eosinophil viability was measured by trypan blue dye exclusion.
  
  
  RESULTS
  Eosinophil survival was prolonged in cultures with recombinant soluble ICAM-1 compared with cultures without it (P <.01 on days 2, 4, and 6); this effect was dose-dependent. Eosinophil survival in cultures with recombinant soluble ICAM-1 was significantly inhibited by antibodies against ICAM-1 (P <.01), complement receptor 3 (P <.01), and lymphocyte function-associated antigen-1beta (P <.01). Anti-IL-3 showed no effect on eosinophil survival, whereas anti-IL-5 caused partial inhibition of survival. Interestingly, anti-granulocyte/macrophage colony-stimulating factor caused the complete inhibition of eosinophil survival in cultures with recombinant soluble ICAM-1.
  
  
  CONCLUSIONS
  These results suggested the importance of the beta2 integrins in eosinophil-mediated allergic inflammation.
authors.affiliation: Department of Clinical and Laboratory Medicine, Akita University School of Medicine, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Chihara
authors.forename: T
authors.initials: T
authors.lastname: Kakazu
authors.forename: I
authors.initials: I
authors.lastname: Higashimoto
authors.forename: N
authors.initials: N
authors.lastname: Saito
authors.forename: K
authors.initials: K
authors.lastname: Honda
authors.forename: S
authors.initials: S
authors.lastname: Sannohe
authors.forename: H
authors.initials: H
authors.lastname: Kayaba
authors.forename: O
authors.initials: O
authors.lastname: Urayama
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004804:Eosinophils / Q000166:cytology*; D006801:Humans; D016023:Integrins / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D012995:Solubility
chemical_list: D016023:Integrins; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1