Abstract
Phosphatidylserine (PS), which is normally located on the inner leaflet of the plasma membrane, translocates to the outer leaflet at the early stage of apoptosis. The PS externalization provides a signal for phagocytes to initiate uptake of apoptotic cells. After phagocytosis of apoptotic cells, phagocytes induce the secretion of anti-inflammatory mediators including prostaglandin E2 (PGE2). PS-containing liposomes (PSLs) can mimic the effects of apoptotic cells on phagocytes to induce the secretion of PGE2. PSLs induce the PGE2 secretion from microglia without induction of either cyclooxygenase (COX)-2 or microsomal prostaglandin E synthase (mPGES)-1. PSLs are found to rather utilize COX-1/mPGES-2 system to produce PGE2 secretion and then shift microglia and macrophages from pro- to anti-inflammatory phenotype by an autocrine action of PGE2. Moreover, PSLs inhibit the maturation of dendritic cells and osteoclast precursors. Therefore, PSLs will be potential pharmacological interventions for inflammatory and immune diseases through feedback mechanism utilizing PGE2.
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Acknowledgments
Studies conducted in our laboratories were supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Science and Culture, Japan (No. 20592174 to Zhou Wu and No. 20390472 to Hiroshi Nakanishi).
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Wu, Z., Nakanishi, H. Phosphatidylserine-Containing Liposomes: Potential Pharmacological Interventions Against Inflammatory and Immune Diseases Through the Production of Prostaglandin E2 After Uptake by Myeloid Derived Phagocytes. Arch. Immunol. Ther. Exp. 59, 195–201 (2011). https://doi.org/10.1007/s00005-011-0123-4
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DOI: https://doi.org/10.1007/s00005-011-0123-4