Phosphatidylserine-containing liposomes: potential pharmacological interventions against inflammatory and immune diseases through the production of prostaglandin E(2) after uptake by myeloid derived phagocytes

Arch Immunol Ther Exp (Warsz). 2011 Jun;59(3):195-201. doi: 10.1007/s00005-011-0123-4. Epub 2011 Apr 10.

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 E(2) (PGE(2)). PS-containing liposomes (PSLs) can mimic the effects of apoptotic cells on phagocytes to induce the secretion of PGE(2). PSLs induce the PGE(2) 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 PGE(2) secretion and then shift microglia and macrophages from pro- to anti-inflammatory phenotype by an autocrine action of PGE(2). 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 PGE(2).

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autocrine Communication
  • Cell Differentiation / drug effects
  • Dinoprostone / metabolism
  • Dinoprostone / pharmacology*
  • Humans
  • Immune System Diseases / immunology
  • Immune System Diseases / therapy*
  • Immunity / drug effects
  • Liposomes / metabolism
  • Liposomes / therapeutic use*
  • Myeloid Cells / pathology
  • Phagocytes / drug effects*
  • Phagocytes / immunology
  • Phagocytes / metabolism
  • Phagocytes / pathology
  • Phosphatidylserines / immunology
  • Phosphatidylserines / metabolism

Substances

  • Liposomes
  • Phosphatidylserines
  • Dinoprostone