title: Liposomal microparticle injection can induce myeloid-derived suppressor cells (MDSC)-like cells in vivo.
abstract: BACKGROUND
  Myeloid-derived suppressor cells (MDSCs) are a subset of immature myeloid cells that function as immunosuppressive cells in various pathological conditions. Membrane-derived microvesicles are thought to be involved in MDSC induction. Earlier reports have described that injection of considerable amount of liposome into rat can suppress Con A-induced splenic T-cell proliferation. Liposome-internalized cells expressing CD11b/c suppress T-cell proliferation. Nitric oxide (NO) appears to be involved in the suppression. We speculated that, similarly to membrane-derived microvesicles, liposomal microparticles can induce MDSC-like cells in vivo.
  
  
  OBJECTIVE
  To confirm our speculation we investigated dose-dependency of the suppressive effect, the effect of liposome on the induction of inducible NO synthase (iNOS), and anti-CD3 antibody-stimulated T-cell proliferation and cytokine production.
  
  
  METHODS
  Liposome particles of 250 nm diameter were prepared and suspended in saline. Then, various amounts of liposomal suspension were injected intravenously into rats. After 24 h, rat spleens were removed and concanavalin A (or anti-CD3 antibody) stimulated-splenic T-cell proliferation and the production of iNOS, NO and cytokines were evaluated.
  
  
  RESULTS
  T-cell proliferation was suppressed dose-dependently by liposome injection. The immunosuppressive cell exerts its suppressive activity in a dose-dependent manner. The suppression was eliminated by iNOS inhibitor. iNOS was detected in liposome-loaded splenocytes. Anti-CD3 antibody-stimulated T-cell proliferation was also inhibited. Enhanced production of IL-10 was observed.
  
  
  CONCLUSIONS
  Liposomal microparticles can induce MDSC-like cells in vivo. The lipids which comprise liposomes might serve an important role in the induction of MDSCs in vivo.
authors.affiliation: a Department of Pediatrics , Asahikawa Medical University , Asahikawa , Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Azuma
authors.affiliation: a Department of Pediatrics , Asahikawa Medical University , Asahikawa , Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: a Department of Pediatrics , Asahikawa Medical University , Asahikawa , Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: a Department of Pediatrics , Asahikawa Medical University , Asahikawa , Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Ishibazawa
authors.affiliation: b Department of Immunopathology , Asahikawa Medical University , Asahikawa , Japan.
authors.forename: Hiroya
authors.initials: H
authors.lastname: Kobayashi
authors.affiliation: c Department of Biochemistry , Nara Medical University , Nara , Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sakai
authors.affiliation: d Japanese Red Cross Hokkaido Block Blood Center , Sapporo, Hokkaido , Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Takahashi
authors.affiliation: d Japanese Red Cross Hokkaido Block Blood Center , Sapporo, Hokkaido , Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Fujihara
mesh_terms: D000818:Animals; D017252:CD3 Complex / Q000276:immunology; D055252:Cell-Derived Microparticles / Q000276:immunology*; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000276:immunology; D008081:Liposomes / Q000494:pharmacology*; D008297:Male; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology*; D009569:Nitric Oxide / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000276:immunology; D051381:Rats; D011921:Rats, Inbred WKY; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
chemical_list: D017252:CD3 Complex; D016207:Cytokines; D008081:Liposomes; D003208:Concanavalin A; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat
keywords: Liposome; MDSC; exosome; extosome; iNOS; microvesicle; nitric oxide