Activation of macrophages from aging mice by detoxified lipid A.
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.
Chen
Y F
YF
Department of Medical Microbiology/Immunology, University of Minnesota, Duluth 55812.
Solem
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L
Johnson
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AG
D000375:Aging; D000818:Animals; D002177:Candidiasis / Q000628:therapy; D006861:Hydrogen Peroxide / Q000378:metabolism; D007111:Immunity, Cellular / Q000187:drug effects; D007167:Immunotherapy; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D051379:Mice; D009113:Muramidase / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010587:Phagocytosis / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism
D008050:Lipid A; D008070:Lipopolysaccharides; D013481:Superoxides; D006861:Hydrogen Peroxide; D009113:Muramidase; C048436:monophosphoryl lipid A