Rhodopseudomonas sphaeroides lipid A derivatives block in vitro induction of tumor necrosis factor and endotoxin tolerance by smooth lipopolysaccharide and monophosphoryl lipid A.
Rhodopseudomonas (Rhodobacter) sphaeroides diphosphoryl lipid A is a relatively inert species of lipid A but has been shown to antagonize the effects of toxic lipopolysaccharide (LPS) both in vivo and in vitro. The antagonist and its monophosphoryl derivative were examined for the ability to block tumor necrosis factor synthesis and reverse tolerance induction in vitro in macrophage cultures stimulated with bioactive preparations of smooth LPS, rough LPS, diphosphoryl lipid A, and monophosphoryl lipid A. Inhibition of agonist activity and reversal of tolerance by these novel penta-acylated lipid A antagonists provides new insight into macrophage-LPS interactions.
Henricson
B E
BE
Department of Microbiology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
Perera
P Y
PY
Qureshi
N
N
Takayama
K
K
Vogel
S N
SN
D000818:Animals; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D008070:Lipopolysaccharides / Q000633:toxicity*; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D012241:Rhodopseudomonas / Q000737:chemistry* / Q000502:physiology; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D008050:Lipid A; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C049596:diphosphoryl lipid A; C048436:monophosphoryl lipid A