The synthetic chemoattractant peptide WKYMVm induces superoxide production by human eosinophils via the phosphoinositide 3-kinase-mediated activation of ERK1/2

Heon Shin Myeong, Young Ah Lee, Yoe Sik Bae, Hirohito Kita, Youngdong Kim, Ho Ryu Sung

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Background: Eosinophils play a key role in allergic inflammation and parasitic infections. The synthetic peptide, Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm), has been previously shown to activate eosinophils and thus to enhance respiratory burst through the formyl peptide receptors. Objective: This study was undertaken to determine the intracellular signaling pathway involved in WKYMVm-stimulated superoxide production by human eosinophils. Methods: Purified eosinophils from peripheral blood were stimulated with various concentrations (10-3 to 10 μM) of WKYMVm and the involvement of Pl3-kinase and MAP kinases in WKYMVm-triggered superoxide production was investigated using pharmacological inhibitors. Results: WKYMVm-induced superoxide production by eosinophils was strongly inhibited by pretreatment with the Pl3-kinase inhibitor LY294002. In addition, pretreatment with the ERK1/2 kinase inhibitor PD98059 resulted in marked inhibition of superoxide production induced by WKYMVm. Indeed, WKYMVm strongly induced phosphorylation of ERK1/2. The ERK1/2 activation by the peptide was transient and peaked after 2 min of stimulation. Furthermore, ERK1/2 activation by WKYMVm was completely inhibited by pretreatment with the Pl3-kinase inhibitor LY294002, but not by the PKC inhibitor Ro-31-8220. Conclusion: These results suggest that WKYMVm stimulates human eosinophils to induce superoxide production via a Pl3-kinase-mediated ERK1/2 pathway.

Original languageEnglish (US)
Pages (from-to)21-26
Number of pages6
JournalInternational archives of allergy and immunology
Volume137
Issue numberSUPPL.
DOIs
StatePublished - 2005

Keywords

  • ERK1/2
  • Eosinophils
  • Phosphoinositide 3-kinase
  • Superoxide
  • WKYMVm

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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