Inhibition of LPS-mediated cell activation in vitro and in vivo by gangliosides

J. J. Mond, K. Witherspoon, Robert K Yu, P. Y. Perera, S. N. Vogel

Research output: Contribution to journalArticle

6 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)57-62
Number of pages6
JournalCirculatory Shock
Volume44
Issue number2
StatePublished - Dec 1 1994
Externally publishedYes

Fingerprint

Gangliosides
Lipopolysaccharides
B-Lymphocytes
Cell Proliferation
In Vitro Techniques
G(M1) Ganglioside
Galactosamine
Ionomycin
Rain
Macrophage Activation
Poisons
Anti-Idiotypic Antibodies
Macrophages
Injections
Membranes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Mond, J. J., Witherspoon, K., Yu, R. K., Perera, P. Y., & Vogel, S. N. (1994). Inhibition of LPS-mediated cell activation in vitro and in vivo by gangliosides. Circulatory Shock, 44(2), 57-62.

Inhibition of LPS-mediated cell activation in vitro and in vivo by gangliosides. / Mond, J. J.; Witherspoon, K.; Yu, Robert K; Perera, P. Y.; Vogel, S. N.

In: Circulatory Shock, Vol. 44, No. 2, 01.12.1994, p. 57-62.

Research output: Contribution to journalArticle

Mond, JJ, Witherspoon, K, Yu, RK, Perera, PY & Vogel, SN 1994, 'Inhibition of LPS-mediated cell activation in vitro and in vivo by gangliosides', Circulatory Shock, vol. 44, no. 2, pp. 57-62.
Mond JJ, Witherspoon K, Yu RK, Perera PY, Vogel SN. Inhibition of LPS-mediated cell activation in vitro and in vivo by gangliosides. Circulatory Shock. 1994 Dec 1;44(2):57-62.
Mond, J. J. ; Witherspoon, K. ; Yu, Robert K ; Perera, P. Y. ; Vogel, S. N. / Inhibition of LPS-mediated cell activation in vitro and in vivo by gangliosides. In: Circulatory Shock. 1994 ; Vol. 44, No. 2. pp. 57-62.
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