Diphosphoryl lipid A from Rhodopseudomonas sphaeroides ATCC 17023 blocks induction of cachectin in macrophages by lipopolysaccharide.
Purified diphosphoryl lipid A (DPLA) obtained from the nontoxic lipopolysaccharide of Rhodopseudomonas sphaeroides ATCC 17023 was shown to block the induction of cachectin (tumor necrosis factor) in the RAW 264.7 macrophage cell line by toxic deep-rough-chemotype lipopolysaccharide (ReLPS) of Escherichia coli in a concentration-dependent manner. The ReLPS-to-DPLA mass ratios of 1:10 and 1:100 (when 1.0 ng of ReLPS per ml was used) gave 55 and 95% inhibitions, respectively, of the induction of cachectin. Since the structure of the DPLA from R. sphaeroides is so similar to that of the lipid A moiety of the toxic ReLPS from E. coli, we suggest that this inhibition could have been due to competitive binding by DPLA to the active sites on the macrophage. This DPLA could become a useful reagent to study the nature of lipopolysaccharide/lipid A binding in macrophages and perhaps other responding cells.
Takayama
K
K
Mycobacteriology Laboratory, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin 53705.
Qureshi
N
N
Beutler
B
B
Kirkland
T N
TN
D000818:Animals; D008050:Lipid A / Q000031:analogs & derivatives* / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology; D051379:Mice; D012242:Rhodobacter sphaeroides / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D008050:Lipid A; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C049596:diphosphoryl lipid A