TY - JOUR
T1 - Enhancement of mast cell survival
T2 - A novel function of some secretory phospholipase A2 isotypes
AU - Fonteh, A. N.
AU - Marion, C. R.
AU - Barham, B. J.
AU - Edens, M. B.
AU - Atsumi, G. I.
AU - Samet, J. M.
AU - High, K. P.
AU - Chilton, F. H.
PY - 2001/10/15
Y1 - 2001/10/15
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.167.8.4161
DO - 10.4049/jimmunol.167.8.4161
M3 - Article
C2 - 11591736
AN - SCOPUS:0035887918
SN - 0022-1767
VL - 167
SP - 4161
EP - 4171
JO - Journal of Immunology
JF - Journal of Immunology
IS - 8
ER -