Abstract
Addition of purified GM1 gangliosides inhibited lipopolysaccharide (LPS)- stimulated proliferation of purified B cells by greater than 90%. Addition of gangliosides to B cells as late as 120 rain after the addition of LPS still inhibited B-cell proliferation, suggesting that inhibition did not simply reflect direct binding of LPS to gangliosides. Gangliosides also inhibited proliferation of B cells stimulated by anti-Ig antibodies, albeit to a lesser degree than inhibition of the LPS-stimulated response. The finding that B- cell proliferation stimulated by the combination of PMA + ionomycin was also inhibited by gangliosides suggests that its inhibitory activity did not reflect interference with binding of the B-cell stimuli to membrane receptors. The inhibitory effect of gangliosides was not restricted to B cells, since LPS-induced TNF production by macrophages was also inhibited in vitro. The inhibitory activity of gangliosides was also seen in vivo, and mice injected with soluble gangliosides or implanted with slow-release pellets impregnated with gangliosides showed reduced TNF production in vivo in response to LPS. Mice that were implanted with these slow-release pellets were also protected from LPS-induced lethality. Thus, while only 10% of control mice survived injection with LPS + galactosamine, the experimental group showed a 64% survival. It is likely that this protective effect reflects the ability of gangliosides to suppress LPS-mediated TNF production. This model provides a basis for studying a regulatory role for gangliosides in B-cell activation in vitro and macrophage activation in vitro and in vivo. Furthermore, it suggests new approaches to suppress the toxic effects induced by LPS in vivo.
Original language | English (US) |
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Pages (from-to) | 57-62 |
Number of pages | 6 |
Journal | Circulatory Shock |
Volume | 44 |
Issue number | 2 |
State | Published - Dec 1 1994 |
Externally published | Yes |
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine