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Liposomal microparticle injection can induce myeloid-derived suppressor cells (MDSC)-like cells in vivo
Hiroshi Azuma1, Yoichiro Yoshida1, Hironori Takahashi1
1a Department of Pediatrics , Asahikawa Medical University , Asahikawa , Japan.
Context:
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.
Objectives:
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.
Materials And 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.
Insights
Liposomal microparticles can induce myeloid-derived suppressor cells (MDSCs) in vivo, suppressing T-cell proliferation. This effect is dose-dependent and mediated by inducible nitric oxide synthase (iNOS).
Area of Science:
- Immunology
- Cell Biology
- Nanomedicine
Background:
- Myeloid-derived suppressor cells (MDSCs) are critical immunosuppressive cells in pathological conditions.
- Membrane-derived microvesicles are implicated in MDSC induction.
- Liposomes are known to suppress T-cell proliferation, with nitric oxide (NO) involvement.
Purpose of the Study:
- To investigate if liposomal microparticles can induce MDSC-like cells in vivo.
- To determine the dose-dependency of liposome-induced immunosuppression.
- To assess liposome effects on inducible NO synthase (iNOS), T-cell proliferation, and cytokine production.
Main Methods:
- Preparation of 250 nm liposome particles and intravenous injection into rats.
- Evaluation of T-cell proliferation (Concanavalin A and anti-CD3 stimulated) 24 hours post-injection.
- Measurement of iNOS, NO, and cytokine production in rat splenocytes.
Main Results:
- Liposome injection suppressed T-cell proliferation in a dose-dependent manner.
- iNOS was detected in liposome-loaded splenocytes, and suppression was abrogated by an iNOS inhibitor.
- Anti-CD3 stimulated T-cell proliferation was inhibited, with enhanced IL-10 production observed.
Conclusions:
- Liposomal microparticles effectively induce MDSC-like cells in vivo.
- The lipids within liposomes play a significant role in inducing MDSCs.
- This suggests a potential therapeutic strategy for modulating immune responses.