Regulation of myeloid derived phagocytes by phosphatidylserine-containing liposomes: Possible involvement of prostaglandin E₂ and the potential therapeutic application

Phosphatidylserine (PS), which is normally located on the inner leaflet of the plasma membrane, translocates to the outer leaflet during early stages of apoptosis,. The externalization of PS provides a signal for phagocytes to initiate uptake of apoptotic cells. After the phagocytosis of apoptotic cells, phagocytes start to secrete anti-inflammatory mediators including prostaglandin E₂ (PGE₂), which act an autocrine manner to control their functions. PS-containing liposomes (PS liposomes) can mimic the effects of apoptotic cells on phagocytes to induce the secretion of PGE₂. PS liposomes induced PGE₂ secretion from microglia without induction of either cyclooxygenase (COX)-2 or microsomal prostaglandin E synthase (mPGES)-1. PS liposomes were found to utilize the COX-1/mPGES-2 system to produce PGE₂ secretion and then shift microglia and macrophages from a pro- to anti-inflammatory phenotype by the autocrine action of PGE₂. Moreover, PS liposomes inhibit the maturation of dendritic cells and osteoclast precursors. Therefore, PS liposomes may be potentially useful as one type of pharmacological intervention for inflammatory and immune diseases through a feedback mechanism involving PGE₂.