Phosphatidylserine-specific phospholipase A(1) stimulates histamine release from rat peritoneal mast cells through production of 2-acyl-1-lysophosphatidylserine

Lysophosphatidylserine (1-acyl-24-lso-PS) has been shown to stimulate hista mine release from rat peritoneal mast cells (RPMC) triggered by Fc epsilon RI (high affinity receptor for IgE) cross-linking, although the precise mec hanism of lyso-PS production has been obscure. In the present study we show that phosphatidylserine-specific. phospholipase A(1), PS-PLA(1), stimulate s histamine release from RPMC through production of 2-acyl-1-lyso-PS in the presence of Fc epsilon RI cross-linker. The potency of 2-acyl-1-lyso-PS wa s almost equal to that of 1-acyl-2-lyso-PS. A catalytically inactive PS-PLA , in which an active serine residue (Ser(166)) was replaced with an alanine residue did not show such activity. sPLA(2)-IIA, another secretory PLA(2) that is capable of producing lyso-PS in vitro, was also a poor histamine in ducer against RPMC. PS-PLA(1) significantly stimulated histamine release fr om crude RPMC, indicating that lyso-PS is mainly derived from cells other t han mast cells. In agreement with this phenomenon, the enzyme stimulated th e histamine release more efficiently when RPMC were mixed with apoptotic Ju rkat cells. Under these conditions, lyso-PS with unsaturated fatty acid was released from the apoptotic cells treated with PS-PLA(1). Finally, heparin , which has affinity for PS-PLA(1) completely blocked. the stimulatory effe ct of the enzyme. In conclusion, PS-PLA(1) may bind to heparan sulfate prot eoglycan, efficiently hydrolyze PS appearing on plasma membranes of apoptot ic cells, and stimulate mast cell activation mediated by 2-acyl-1-lyso-PS.