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Published on: April 29, 2015
Murine peritoneal macrophage gangliosides inhibit lymphocyte proliferation
1Infectious Disease Section, West Haven Veterans Administration Medical Center, Connecticut.
Insights
Macrophage gangliosides, in nanogram amounts, significantly inhibit lymphocyte proliferation, acting as potent immunoregulatory agents. This discovery offers new insights into immune modulation distinct from brain gangliosides.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Gangliosides are known immunoregulatory agents affecting lymphocyte proliferation.
- Previous studies primarily used brain gangliosides at high concentrations.
- The role of endogenous macrophage gangliosides in immune regulation was unexplored.
Purpose of the Study:
- To investigate the immunoregulatory effects of endogenous gangliosides purified from murine macrophages.
- To determine if macrophage gangliosides can modulate lymphocyte proliferation in response to mitogens.
Main Methods:
- Purification of gangliosides from thioglycolate-elicited murine peritoneal macrophages.
- Addition of purified macrophage gangliosides to cultures of murine lymphocytes (splenocytes and B lymphocytes).
- Assessment of DNA synthesis and proliferation in response to lipopolysaccharide (LPS) and concanavalin A (ConA).
Main Results:
- Nanogram quantities of macrophage gangliosides profoundly inhibited LPS-induced DNA synthesis in splenocytes and B lymphocytes.
- Macrophage gangliosides also inhibited concanavalin A-mediated lymphocyte proliferation.
- The inhibitory effect was observed across a range of LPS doses and was distinct from asialo-GM1.
- Inhibition was rapid, partially reversible, and occurred without demonstrable cellular toxicity.
Conclusions:
- Endogenous macrophage gangliosides act as potent negative modulators of lymphocyte proliferation.
- These findings reveal a novel immunoregulatory role for macrophage-derived gangliosides, distinct from brain gangliosides.
- Macrophage gangliosides represent a promising target for modulating immune responses.
Abstract:
Gangliosides have been shown to act as immunoregulatory agents by altering proliferative responses of lymphocytes to both antigens and mitogens. Most early studies have utilized brain gangliosides and have required high concentrations. The role of endogenous gangliosides from macrophages has remained unexplored. In this study, thioglycolate-elicited murine peritoneal macrophage gangliosides were purified and added to cultures of murine lymphocytes. Nanogram amounts caused a profound inhibition of LPS-induced DNA synthesis of splenocytes and of purified B lymphocytes, without demonstrable cellular toxicity. No effect was seen using asialo-GM1. This effect was present across a wide range of lipopolysaccharide (LPS) doses. Nanogram amounts of macrophage gangliosides also inhibited concanavalin A (ConA)-mediated lymphocyte proliferation. Inhibition of LPS-induced mitogenesis was present even if gangliosides were removed from the extracellular environment after 15-60 min of incubation prior to the addition of LPS. This inhibition was reversible with incubation of ganglioside pre-treated lymphocytes in medium containing serum. These inhibitory properties of macrophage gangliosides are distinct from those found in studies using brain gangliosides, and support a potential role for macrophage gangliosides as negative modulators of lymphocyte proliferation.
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