Mechanisms that account for the selective release of arachidonic acid from intact cells by secretory phospholipase A₂

The current study examined mechanisms that account for the selective release of arachidonic acid (AA) from cells by secretory phospholipase A₂ (sPLA₂). Initial studies demonstrated that low concentrations of group I and group III PLA₂ isotypes and an sPLA₂-enriched extract from bone marrow-derived mast cells (BMMC) selectively released AA from mast cells. Much higher concentrations of group II PLA₂ were required to release comparable quantities of AA. Group I PLA₂ also selectively released AA from another mast cell line (CFTL-15) and a monocytic cell line (THP-1). In contrast, high concentrations of group I PLA₂ were required to release fatty acids from a promyelocytic cell line (HL-60) and this release was not selective for AA. Binding studies revealed that cell types (BMMC, CFTL-15 and THP-1) which selectively released AA also had the capacity to specifically bind group I PLA₂. However, group II PLA₂, which did not selectively release AA from cells, also did not specifically bind to these same cell types. Additional studies revealed that sPLA₂ binding to the mast cell receptor was attenuated after stimulation with antigen or ionophore A23187. Reverse transcriptase-polymerase chain reaction analyses indicated the presence of mRNA for the sPLA₂ receptor in BMMC, CFTL-15 and THP-1 and the absence of this mRNA in HL-60. Final studies demonstrated that p-aminophenyl-α-d-mannopyranoside BSA, a known ligand of the sPLA₂ receptor, also selectively released AA from mast cells but not from HL-60 cells. These experiments indicated that receptor occupancy alone (without PLA₂ activity) is sufficient to induce the release of AA from mast cells. Together, these data reveal that specific isotypes of sPLA₂ have the capacity to selectively release AA from certain cells by their capacity to bind to sPLA₂ receptors on the cell surface. Copyright (C) 1998 Elsevier Science B.V.