Azuma Hiroshi, Yoshida Yoichiro, Takahashi Hironori, Ishibazawa Emi, Kobayashi Hiroya, Sakai Hiromi, Takahashi Daisuke, Fujihara Mitsuhiro
a Department of Pediatrics , Asahikawa Medical University , Asahikawa , Japan.
b Department of Immunopathology , Asahikawa Medical University , Asahikawa , Japan.
Immunopharmacol Immunotoxicol. 2017 Jun;39(3):140-147. doi: 10.1080/08923973.2017.1306867. Epub 2017 Apr 5.
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.
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.
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.
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.
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.
髓源性抑制细胞（MDSCs）是未成熟髓细胞的一个亚群，在各种病理条件下发挥免疫抑制细胞的作用。膜衍生的微泡被认为参与了MDSC的诱导。早期报告描述，向大鼠注射大量脂质体可抑制刀豆蛋白A诱导的脾T细胞增殖。内化脂质体的表达CD11b/c的细胞可抑制T细胞增殖。一氧化氮（NO）似乎参与了这种抑制作用。我们推测，与膜衍生的微泡类似，脂质体微粒可在体内诱导MDSC样细胞。
为证实我们的推测，我们研究了抑制作用的剂量依赖性、脂质体对诱导型一氧化氮合酶（iNOS）诱导的影响以及抗CD3抗体刺激的T细胞增殖和细胞因子产生。
制备直径为250nm的脂质体颗粒并悬浮于盐水中。然后，将不同量的脂质体悬浮液静脉注射到大鼠体内。24小时后，取出大鼠脾脏，评估刀豆球蛋白A（或抗CD3抗体）刺激的脾T细胞增殖以及iNOS、NO和细胞因子的产生。
脂质体注射剂量依赖性地抑制T细胞增殖。免疫抑制细胞以剂量依赖方式发挥其抑制活性。iNOS抑制剂可消除这种抑制作用。在负载脂质体的脾细胞中检测到iNOS。抗CD3抗体刺激的T细胞增殖也受到抑制。观察到IL-10的产生增加。
脂质体微粒可在体内诱导MDSC样细胞。构成脂质体的脂质可能在体内MDSCs的诱导中起重要作用。
