Enhancement of mast cell survival: A novel function of some secretory phospholipase A2 isotypes

A. N. Fonteh, C. R. Marion, B. J. Barham, M. B. Edens, G. I. Atsumi, J. M. Samet, K. P. High, F. H. Chilton

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

This study tested the hypothesis that certain secretory phospholipase A2 (sPLA2) isotypes act in a cytokine-like fashion through cell surface receptors to influence mast cell survival. Initial experiments revealed that sPLA2 activity and sPLA2 receptor expression are increased, and mast cells lost their capacity to maintain membrane asymmetry upon cytokine depletion. Groups IB and III, but not group IIA PLA2, prevented the loss of membrane asymmetry. Similarly, group IB prevented nucleosomal DNA fragmentation in mast cells. Providing putative products of sPLA2 hydrolysis to cytokine-depleted mast cells did not influence survival. Furthermore, catalytic inactivation of sPLA2 did not alter its capacity to prevent apoptosis. Inhibition of protein synthesis using cycloheximide or actinomycin reversed the antiapoptotic effect of sPLA2. Additionally, both wild-type and catalytically inactive group IB PLA2 induced IL-3 synthesis in mast cells. However, adding IL-3-neutralizing Ab did not change Annexin VFITC binding and only partially inhibited thymidine incorporation in sPLA2-supplemented mast cells. In contrast, IL-3-neutralizing Ab inhibited both Annexin VFITC binding and thymidine incorporation in mast cells maintained with IL-3. sPLA2 enhanced phosphoinositide 3′-kinase activity, and a specific inhibitor of phosphoinositide 3′-kinase reversed the antiapoptotic effects of sPLA2 Likewise, sPLA2 increased the degradation of I-κBα, and specific inhibitors of nuclear factor κ activation (NF-κB) reversed the antiapoptotic effects of sPLA2. Together, these experiments reveal that certain isotypes of sPLA2 enhance the survival of mast cells in a cytokine-like fashion by activating antiapoptotic signaling pathways independent of IL-3 and probably via sPLA2 receptors rather than sPLA2 catalytic products.

Original languageEnglish (US)
Pages (from-to)4161-4171
Number of pages11
JournalJournal of Immunology
Volume167
Issue number8
DOIs
StatePublished - Oct 15 2001
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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