Different functional aspects of the group II subfamily (types IIA and V) and type X secretory phospholipase A(2)s in regulating arachidonic acid release and prostaglandin generation - Implications of cyclooxygenase-2 induction and phospholipid scramblase-mediated cellular membrane perturbation

We have recently reported that members of the heparin-binding group II subf amily of secretory PLL(2)s (sPLA(2)s) (types IIA and V), when transfected i nto 293 cells, released [H-3]arachidonic acid (AA) preferentially in respon se to interleukin-l (IL-1) and acted as "signaling" PLA(2)s that were funct ionally coupled with prostaglandin biosynthesis. Here we show that these gr oup II subfamily sPLA(2)s and the type X sPLA(2) behave in a different mann er, the former being more efficiently coupled with the prostaglandin-biosyn thetic pathway than the latter, in 293 transfectants. Type X sPLA(2) which bound only minimally to cell surface proteoglycans, augmented the release o f both [H-3]AA and [H-3]oleic acid in the presence of serum but not IL-l. B oth types IIA and V sPLA(2) the AA released by which was efficiently conver ted to prostaglandin E-2, markedly augmented IL-1-induced expression of cyc looxygenase (COX)-2 in a heparin-sensitive fashion, whereas type X sPLA(2) lacked the ability to augment COX-2 expression, thereby exhibiting the poor prostaglandin E-2-biosynthetic response unless either of the COX isozymes was forcibly introduced into type X sPLA(2)-expressing cells. Implication o f phospholipid scramblase, an enzyme responsible for the perturbation of pl asma membrane asymmetry, revealed that the scramblase-transfected cells bec ame more sensitive to types IIA and V, but not X, sPLA(2), releasing both [ H-3]AA and [H-3]oleic acid in an IL-1-independent manner. Thus, although ph ospholipid scramblase-mediated alteration in plasma membrane asymmetry actu ally led to the increased cellular susceptibility to the group II subfamily of sPLA(2)s, several lines of evidence suggest that it does not entirely m imic their actions on cells after IL-1 signaling. Interestingly, coexpressi on of type IIA or V, but not X, sPLA(2) and phospholipid scramblase resulte d in a marked reduction in cell growth, revealing an unexplored antiprolife rative aspect of particular classes of sPLA(2).