Kanda N, Tamaki K
Department of Dermatology, Faculty of Medicine, University of Tokyo, Japan.
J Allergy Clin Immunol. 1998 Nov;102(5):813-20. doi: 10.1016/s0091-6749(98)70022-3.
Gangliosides are glycosphingolipids that contain sialic acid and have various immunomodulatory effects.
We studied in vitro effects of gangliosides on human humoral immune responses.
PBMCs from healthy volunteers were cultured with gangliosides GM1, GM2, GM3, GD1a, GD1b, GD2, GD3, GT1b, and GQ1b. The amounts of IgG, IgM, and IgA and cytokine activity in the culture supernatants were measured with use of an ELISA. Proliferation was determined by [3H] thymidine uptake.
Among the various gangliosides tested, GQ1b most strongly enhanced spontaneous IgG, IgM, and IgA production by human PBMCs. The effect of GQ1b was revealed at 0.1 micromol/L, increased dose dependently, and was maximized at 10 micromol/L. Weaker but significant stimulatory effects on the Ig production were manifested by GM2 and GD1a, whereas GT1b and GD1b were inhibitory. None of the gangliosides examined affected the proliferation of PBMCs. GQ1b did not enhance Ig production of B cells alone. Anti-IL-6 and anti-IL-10 antibody each partially blocked GQ1b-induced enhancement of the Ig production by PBMCs, and the addition of both antibodies completely blocked the enhancement. GQ1b enhanced both IL-6 and IL-10 production of T cells without affecting those of monocytes or B cells. GQ1b enhanced Ig production of T and B cell culture without monocytes. When T cells were preincubated with GQ1b, washed and added to B cells and monocytes, and then cultured together, the Ig production was also enhanced, although to a lesser extent than the whole time incubation. Exogenous IL-6 and IL-10 each enhanced Ig production of B cells alone, and the addition of both gave additive effects.
These results suggest that GQ1b may indirectly enhance Ig production of B cells by promoting IL-6 and IL-10 production of T cells in whole PBMC culture. That GQ1b may act as an important immunostimulator is also indicated.
神经节苷脂是含有唾液酸的糖鞘脂，具有多种免疫调节作用。
我们研究了神经节苷脂对人体液免疫反应的体外作用。
将来自健康志愿者的外周血单个核细胞（PBMCs）与神经节苷脂GM1、GM2、GM3、GD1a、GD1b、GD2、GD3、GT1b和GQ1b一起培养。使用酶联免疫吸附测定法（ELISA）测量培养上清液中IgG、IgM和IgA的量以及细胞因子活性。通过[3H]胸苷摄取来测定增殖情况。
在测试的各种神经节苷脂中，GQ1b最强烈地增强了人PBMCs自发产生的IgG、IgM和IgA。GQ1b在0.1微摩尔/升时显示出作用，呈剂量依赖性增加，在10微摩尔/升时达到最大值。GM2和GD1a对Ig产生有较弱但显著的刺激作用，而GT1b和GD1b具有抑制作用。所检测的神经节苷脂均未影响PBMCs的增殖。GQ1b单独不能增强B细胞的Ig产生。抗IL - 6和抗IL - 10抗体各自部分阻断了GQ1b诱导的PBMCs Ig产生增强，同时添加两种抗体则完全阻断了这种增强。GQ1b增强了T细胞的IL - 6和IL - 10产生，而不影响单核细胞或B细胞的产生。GQ1b增强了无单核细胞的T和B细胞培养物中的Ig产生。当T细胞先用GQ1b预孵育、洗涤后加入B细胞和单核细胞，然后一起培养时，Ig产生也增强了，尽管程度低于全程孵育。外源性IL - 6和IL - 10各自单独增强了B细胞的Ig产生，同时添加两者具有相加作用。
这些结果表明，在整个PBMC培养中，GQ1b可能通过促进T细胞产生IL - 6和IL - 10来间接增强B细胞的Ig产生。这也表明GQ1b可能作为一种重要的免疫刺激剂。
