Phosphatidylserine-specific Phospholipase A1 Stimulates Histamine Release from Rat Peritoneal Mast Cells through Production of 2-Acyl-1-lysophosphatidylserine

Hiroyuki Hosono, Junken Aoki, Yuki Nagai, Koji Bandoh, Mayuko Ishida, Ryo Taguchi, Hiroyuki Arai, Keizo Inoue

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56 Citations (Scopus)

Abstract

Lysophosphatidylserine (1-acyl-2-lyso-PS) has been shown to stimulate histamine release from rat peritoneal mast cells (RPMC) triggered by FcεRI (high affinity receptor for IgE) cross-linking, although the precise mechanism of lyso-PS production has been obscure. In the present study we show that phosphatidylserine-specific phospholipase A1, PS-PLA1, stimulates histamine release from RPMC through production of 2-acyl-1-lyso-PS in the presence of FcεRI cross-linker. The potency of 2-acyl-1-lyso-PS was almost equal to that of 1-acyl-2-lyso-PS. A catalytically inactive PS-PLA 1, in which an active serine residue (Ser166) was replaced with an alanine residue did not show such activity. sPLA 2-IIA, another secretory PLA2 that is capable of producing lyso-PS in vitro, was also a poor histamine inducer against RPMC. PS-PLA1 significantly stimulated histamine release from crude RPMC, indicating that lyso-PS is mainly derived from cells other than mast cells. In agreement with this phenomenon, the enzyme stimulated the histamine release more efficiently when RPMC were mixed with apoptotic Jurkat cells. Under these conditions, lyso-PS with unsaturated fatty acid was released from the apoptotic cells treated with PS-PLA1. Finally, heparin, which has affinity for PS-PLA1, completely blocked the stimulatory effect of the enzyme. In conclusion, PS-PLA1 may bind to heparan sulfate proteoglycan, efficiently hydrolyze PS appearing on plasma membranes of apoptotic cells, and stimulate mast cell activation mediated by 2-acyl-1-lyso-PS.

Original languageEnglish
Pages (from-to)29664-29670
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number32
DOIs
Publication statusPublished - 2001 Aug 10

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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