Mast cells enhance eosinophil survival in vitro: Role of TNF-α and granulocyte-macrophage colony-stimulating factor

Francesca Levi-Schaffer*, Vladislav Temkin, Vivian Malamud, Sari Feld, Yael Zilberman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

117 Scopus citations

Abstract

Mast cell-eosinophil interactions in allergy have not yet been completely defined. To determine whether mast cells influence eosinophil survival, human peripheral blood eosinophils were incubated with rat peritoneal mast cell sonicate. After 3 days, viable eosinophils in medium were 21.3% compared with 44% with mast cell sonicate. Like sonicate, supernatants of compound 48/80-activated mast cells enhanced eosinophil survival, demonstrating that the factor(s) involved is stored preformed and rapidly released. Increased eosinophil survival was due to an inhibition of apoptosis (morphologic analysis; annexin V/PI). Neutralizing Abs to granulocyte-macrophage CSF (GM-CSF), but not to IL-3 or IL-5, decreased by 61.7% the enhancing effect on eosinophil viability. Eosinophils are the source of GM-CSF since its release in the culture medium was inhibited by their incubation with the mast cell sonicate together with dexamethasone. In addition, eosinophils incubated with the sonicate expressed mRNA for GM-CSF. To partially characterize the mast cell-derived factor(s) increasing eosinophil survival, the sonicate was heated (56°C/30 min or 100°C/10 min) or preincubated with antihistamines or with anti-TNF-α-neutralizing Abs. Most of the activity was heat labile. TNF-α was found to be predominantly (70%) responsible, while histamine had no role. Mast cell sonicate also caused eosinophils to release eosinophil peroxidase and to display morphologic signs of activation. In conclusion, we have demonstrated that mast cells enhance eosinophil survival in part through their activation to produce and release the autocrine survival cytokine GM-CSF.

Original languageAmerican English
Pages (from-to)5554-5562
Number of pages9
JournalJournal of Immunology
Volume160
Issue number11
StatePublished - 1 Jun 1998

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