Phosphatidylserine-specific Phospholipase A1Stimulates Histamine Release from Rat Peritoneal Mast Cells through Production of 2-Acyl-1-lysophosphatidylserine

Abstract

Lysophosphatidylserine (1-acyl-2-lyso-PS) has been shown to stimulate histamine release from rat peritoneal mast cells (RPMC) triggered by Fc⑀RI (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 A 1 , PS-PLA 1 , stimulates histamine release from RPMC through production of 2-acyl-1-lyso-PS in the presence of Fc⑀RI 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 (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 inducer against RPMC. PS-PLA 1 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-PLA 1 . Finally, heparin, which has affinity for PS-PLA 1 , completely blocked the stimulatory effect of the enzyme. In conclusion, PS-PLA 1 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.

NADPH Oxidase-dependent Generation of Lysophosphatidylserine Enhances Clearance of Activated and Dying Neutrophils via G2A

“…Lyso-PS Are Abundant Modified PS Species Generated in Neutrophils Stimulated to Activate the NADPH Oxidase-The signaling potential of lyso-PS was first recognized in its description as a potent mast cell secretagogue, and it has subsequently been given signaling roles in other settings (20,21,39,55,56). Here, we have shown that lyso-PS species were generated in vitro and in vivo as major modified PS species in neutrophils stimulated to activate the NADPH oxidase.…”

Separation and quantification of 2-acyl-1-lysophospholipids and 1-acyl-2-lysophospholipids in biological samples by LC-MS/MS

“…We chose PS-PLA 1 as an enzyme to produce 2-acyl-1-LysoPS on the cell surface. PS-PLA 1 specifi cally cleaves PS and is capable of cleaving PS on the outer surface of plasma membrane without any effect on cell viability ( 15 ). When HEK293 cells were treated with recombinant PS-PLA 1 , a signifi cant amount of 2-oleoyl-1-LysoPS and a lesser amount of 2-DHA-1-LysoPS were detected in the cells but not in the cell supernatant.…”

The lipase gene family

“…This is even more true of another member of the lipase gene family, phosphatidylserine phospholipase A1, which has an absolute preference for phosphatidylserine and lysophosphatidylserine (10). The function of these two lipases is uncertain at this time, though endothelial lipase is believed to have a role in HDL metabolism (7)(8)(9), while phosphatidylserine phospholipase A1, produced by platelets, may act in response to apoptotic conditions by stimulating mast cell histamine release, thereby contributing to inflammation (25,26).…”