HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fonteh, A. N. Articles by Chilton, F. H. Search for Related Content PubMed PubMed Citation Articles by Fonteh, A. N. Articles by Chilton, F. H. Pubmed/NCBI databases Compound via MeSH Substance via MeSH

Enhancement of Mast Cell Survival: A Novel Function of Some Secretory Phospholipase A₂ Isotypes¹

Alfred N. Fonteh^2,*, Chad R. Marion^*, Brooke J. Barham^*, Michelle B. Edens^*, Gen-ichi Atsumi, James M. Samet, Kevin P. High and Floyd H. Chilton^*,

^* Department of Internal Medicine, Section on Pulmonary and Critical Care Medicine, Divisions of Infectious Diseases, and Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC 27157; and Human Studies Division, National Health and Environmental Effects Research Laboratory, Chapel Hill, NC 27599

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 V^FITC binding and only partially inhibited thymidine incorporation in sPLA₂-supplemented mast cells. In contrast, IL-3-neutralizing Ab inhibited both Annexin V^FITC 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-B, and specific inhibitors of nuclear factor activation (NF-B) 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.

This article has been cited by other articles:

				D Shoseyov, H Bibi, S Offer, O Schwob, M Krimsky, M Kleiman, and S Yedgar Treatment of ovalbumin-induced experimental allergic bronchitis in rats by inhaled inhibitor of secretory phospholipase A2 Thorax, September 1, 2005; 60(9): 747 - 753. [Abstract] [Full Text] [PDF]

				F. Granata, A. Petraroli, E. Boilard, S. Bezzine, J. Bollinger, L. Del Vecchio, M. H. Gelb, G. Lambeau, G. Marone, and M. Triggiani Activation of Cytokine Production by Secreted Phospholipase A2 in Human Lung Macrophages Expressing the M-Type Receptor J. Immunol., January 1, 2005; 174(1): 464 - 474. [Abstract] [Full Text] [PDF]

				M. Triggiani, F. Granata, B. Balestrieri, A. Petraroli, G. Scalia, L. Del Vecchio, and G. Marone Secretory Phospholipases A2 Activate Selective Functions in Human Eosinophils J. Immunol., March 15, 2003; 170(6): 3279 - 3288. [Abstract] [Full Text] [PDF]