Signaling through the beta2 integrin prolongs eosinophil survival

J Allergy Clin Immunol. 2000 Jul;106(1 Pt 2):S99-103. doi: 10.1067/mai.2000.106884.

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.

Conclusion: These results suggested the importance of the beta2 integrins in eosinophil-mediated allergic inflammation.

MeSH terms

  • Cell Survival / drug effects
  • Cells, Cultured
  • Eosinophils / cytology*
  • Humans
  • Integrins / physiology*
  • Intercellular Adhesion Molecule-1 / pharmacology
  • Recombinant Proteins / pharmacology
  • Signal Transduction
  • Solubility

Substances

  • Integrins
  • Recombinant Proteins
  • Intercellular Adhesion Molecule-1