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

43 Citations (Scopus)

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

Fingerprint

Secretory Phospholipase A2
Eosinophils
Group X Phospholipases A2
Arachidonic Acid
Lysophospholipids
Arachidonate 5-Lipoxygenase
Chemical activation
Phosphatidylcholines
Asthma
N-Formylmethionine Leucyl-Phenylalanine
Leukotriene C4
Lysophosphatidylcholines
Phosphorylation
cysteinyl-leukotriene
Mitogen-Activated Protein Kinase Kinases
p38 Mitogen-Activated Protein Kinases
Phosphatidylinositols
Transcriptional Activation
Amplification
Phospholipids

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Lai, Y., Oslund, R. C., Bollinger, J. G., Henderson, W. R., Santana, L. F., Altemeier, W. A., ... 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

Eosinophil cysteinyl leukotriene synthesis mediated by exogenous secreted phospholipase A2 group X. / Lai, Ying; Oslund, Rob C.; Bollinger, James G.; Henderson, William R.; Santana, Luis Fernando; Altemeier, William A.; Gelb, Michael H.; Hallstrand, Teal S.

In: Journal of Biological Chemistry, Vol. 285, No. 53, 31.12.2010, p. 41491-41500.

Research output: Contribution to journalArticle

Lai, Y, Oslund, RC, Bollinger, JG, Henderson, WR, Santana, LF, Altemeier, WA, Gelb, MH & Hallstrand, TS 2010, 'Eosinophil cysteinyl leukotriene synthesis mediated by exogenous secreted phospholipase A2 group X', Journal of Biological Chemistry, vol. 285, no. 53, pp. 41491-41500. https://doi.org/10.1074/jbc.M110.153338
Lai, Ying ; Oslund, Rob C. ; Bollinger, James G. ; Henderson, William R. ; Santana, Luis Fernando ; Altemeier, William A. ; Gelb, Michael H. ; Hallstrand, Teal S. / Eosinophil cysteinyl leukotriene synthesis mediated by exogenous secreted phospholipase A2 group X. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 53. pp. 41491-41500.
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