N Kanda1, K Tamaki. 1. Department of Dermatology, Faculty of Medicine, University of Tokyo, Japan.
Abstract
BACKGROUND: Gangliosides are glycosphingolipids that contain sialic acid and have various immunomodulatory effects. OBJECTIVE: We studied in vitro effects of gangliosides on human humoral immune responses. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND:Gangliosides are glycosphingolipids that contain sialic acid and have various immunomodulatory effects. OBJECTIVE: We studied in vitro effects of gangliosides on human humoral immune responses. METHODS: PBMCs from healthy volunteers were cultured with gangliosidesGM1, 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. RESULTS: 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. CONCLUSION: 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.