Signaling through the beta2 integrin prolongs eosinophil survival.
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.
Chihara
J
J
Department of Clinical and Laboratory Medicine, Akita University School of Medicine, Japan.
Kakazu
T
T
Higashimoto
I
I
Saito
N
N
Honda
K
K
Sannohe
S
S
Kayaba
H
H
Urayama
O
O
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
D016023:Integrins; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1