Possible involvement of aiPLA₂ in the phosphatidylserine-containing liposomes induced production of PGE₂ and PGD₂ in microglia

Liposomes containing phosphatidylserine (PSL) produce PGE₂ after being phagocytosed by microglia, but the precise underlying mechanism behind it still remains unclear. Here, we showed that liposomes consisting of phosphatidylserine and lysophosphatidylcholine, a lipolysis product of phosphatidylcholine by PLA₂, were phagocytosed by microglia, but failed to induce secretion of PGE₂. Furthermore, PSL-induced PGE₂ secretion was significantly inhibited by MJ33, an aiPLA₂ inhibitor, but not by AACOCF₃, a cPLA₂ inhibitor. PSL also produced PGD₂ and 15d-PGJ₂ in microglia. We thus hypothesize that free arachidonic acid is supplied through aiPLA₂-mediated lipolysis of phagocytosed phosphatidylcholine, leading to the production of PGH₂ and its downstream metabolites.