Eosinophil cysteinyl leukotriene synthesis mediated by exogenous secreted phospholipase A2 group X

Ying Lai, Rob C. Oslund, James G. Bollinger, William R. Henderson, Luis Fernando Santana, William A. Altemeier, Michael H. Gelb, Teal S. Hallstrand

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Secreted phospholipase A2 group X (sPLA2-X) has recently been identified in the airways of patients with asthma and may participate in cysteinyl leukotriene (CysLT; C4, D4, and E4) synthesis. We examined CysLT synthesis and arachidonic acid (AA) and lysophospholipid release by eosinophils mediated by recombinant human sPLA2-X. We found that recombinant sPLA2-X caused marked AA release and a rapid onset of CysLT synthesis in human eosinophils that was blocked by a selective sPLA2-X inhibitor. Exogenous sPLA 2-X released lysophospholipid species that arise from phospholipids enriched in AA in eosinophils, including phosphatidylcholine, phosphatidylinositol, and phosphatidylethanolamine as well as plasmenyl phosphatidylcholine and phosphatidylethanolamine. CysLT synthesis mediated by sPLA2-X but not AA release could be suppressed by inhibition of cPLA2α. Exogenous sPLA2-X initiated Ser 505 phosphorylation of cPLA2α, an intracellular Ca2+ flux, and translocation of cPLA2α and 5-lipoxygenase in eosinophils. Synthesis of CysLTs in response to sPLA 2-X or lysophosphatidylcholine was inhibited by p38 or JNK inhibitors but not by a MEK 1/2 inhibitor. A further increase in CysLT synthesis was induced by the addition of sPLA2-X to eosinophils under conditions of N-formyl-methionyl- leucyl-phenylalanine-mediated cPLA2α activation. These results indicate that sPLA2-X participates in AA and lysophospholipid release, resulting in CysLT synthesis in eosinophils through a mechanism involving p38 and JNK MAPK, cPLA2α, and 5-lipoxygenase activation and resulting in the amplification of CysLT synthesis during cPLA2α activation. Transactivation of eosinophils by sPLA2-X may be an important mechanism leading to CysLT formation in the airways of patients with asthma.

Original languageEnglish (US)
Pages (from-to)41491-41500
Number of pages10
JournalJournal of Biological Chemistry
Volume285
Issue number53
DOIs
StatePublished - Dec 31 2010
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Fingerprint Dive into the research topics of 'Eosinophil cysteinyl leukotriene synthesis mediated by exogenous secreted phospholipase A2 group X'. Together they form a unique fingerprint.

  • Cite this

    Lai, Y., Oslund, R. C., Bollinger, J. G., Henderson, W. R., Santana, L. F., Altemeier, W. A., Gelb, M. H., & Hallstrand, T. S. (2010). Eosinophil cysteinyl leukotriene synthesis mediated by exogenous secreted phospholipase A2 group X. Journal of Biological Chemistry, 285(53), 41491-41500. https://doi.org/10.1074/jbc.M110.153338