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Activation of macrophages from aging mice by detoxified lipid A
Y F Chen1, L Solem, A G Johnson
1Department of Medical Microbiology/Immunology, University of Minnesota, Duluth 55812.
Abstract:
A detoxified derivative of endotoxic lipopolysaccharides (LPS), monophosphoryl lipid A (MPL), which is capable of inducing nonspecific resistance against several infectious organisms, was tested for its capacity to activate peritoneal macrophages (M phi) from young and immunodeficient aging BALB/c and C3H/HeN mice. Superoxide generation and hydrogen peroxide release by M phi from aging mice were elevated following intraperitoneal injection with 25 micrograms of LPS or MPL, although they did not reach the peak levels achieved in LPS or MPL-treated young mice. Nitroblue tetrazolium reduction (NBT) by peritoneal M phi from aging C3H/HeN mice treated with MPL was higher than that in control aging mice, equalling that from MPL-treated young mice. LPS, its toxic counterpart, however, failed to increase NBT reduction in either group. MPL enhanced lysozyme activity in M phi from both aging and young C3H/HeN mice above initial control levels. On the other hand, LPS suppressed lysozyme activity in M phi from young, but not aging mice. Phagocytosis of Candida albicans by M phi from BALB/c mice was increased in both groups when stimulated by MPL, but not LPS. Similarly, MPL enhanced the ability to kill Candida in both aging and young BALB/c mice. This effect was not seen with LPS. Thus, a detoxified derivative of LPS was found capable of activating the respiratory burst, NBT reduction, elevating lysozyme activity, as well as phagocytosis and killing of Candida in murine peritoneal M phi from both young and aging mice.
Insights
Monophosphoryl lipid A (MPL), a detoxified lipopolysaccharide derivative, activates immune cells in aging mice. MPL enhances macrophage functions like superoxide generation and Candida killing, suggesting potential for immune support in aged populations.
Area of Science:
- Immunology
- Microbiology
- Aging Research
Background:
- Lipopolysaccharides (LPS) are potent immune stimulators but also toxic.
- Monophosphoryl lipid A (MPL) is a detoxified LPS derivative known to induce resistance against infections.
- Aging is associated with immunodeficiency, impacting macrophage function.
Purpose of the Study:
- To investigate the capacity of MPL to activate peritoneal macrophages (M phi) in young and aging mice.
- To compare the effects of MPL and LPS on macrophage functions in different age groups.
- To assess MPL's potential in enhancing immune responses in immunodeficient aging mice.
Main Methods:
- Peritoneal macrophages were isolated from young and aging BALB/c and C3H/HeN mice.
- Mice were injected intraperitoneally with LPS or MPL.
- Macrophage activation was assessed by measuring superoxide generation, hydrogen peroxide release, Nitroblue tetrazolium (NBT) reduction, lysozyme activity, and phagocytosis/killing of Candida albicans.
Main Results:
- MPL and LPS elevated superoxide generation and hydrogen peroxide release in aging mice, though to a lesser extent than in young mice.
- MPL increased NBT reduction and lysozyme activity in aging mice, while LPS did not.
- MPL enhanced phagocytosis and killing of Candida albicans in peritoneal macrophages from both young and aging mice, an effect not observed with LPS.
Conclusions:
- MPL effectively activates peritoneal macrophages in both young and aging mice.
- MPL stimulates key macrophage functions, including the respiratory burst, NBT reduction, and antimicrobial activity, even in immunodeficient aging mice.
- MPL demonstrates potential as an immune-modulating agent for enhancing host defense in aging populations.