The effect of endotoxin lipopolysaccharide from different bacterial species on the generation of intracellular inositol trisphosphate and superoxide in a human phagocytic cell line.
The acute effects of endotoxins and lipid A on two intracellular responses, inositol phosphate generation and superoxide production were analysed in the DMSO differentiated premyelocytic leukaemic HL-60 cell line. Short-term incubation (1-10 min) with Escherichia coli-type LPS, Salmonella-type LPS and Lipid A caused significant increases in cellular InsP1 and InsP3, compared with control cells (P less than 0.5-P less than 0.001). The Escherichia coli-type LPS released approximately twice the quantity of InsP3 compared with Salmonella-type LPS (P less than 0.001). Lipid A-dependent stimulation of InsP3 production was also detected. The rate of superoxide production increased 1-10 min after addition of both Escherichia coli- and Salmonella-type LPS and Lipid A. Endotoxins and Lipid A caused a dose-dependent increase in intracellular oxidative activity. The superoxide response showed less species dependence and a higher response to particulate lipid A compared with the inositol phosphate response.
Qu
J M
JM
Department of Pharmacology, University of Edinburgh, U.K.
Leaver
H A
HA
Aldhous
M C
MC
Yap
P L
PL
D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology; D008050:Lipid A / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D010586:Phagocytes / Q000187:drug effects* / Q000378:metabolism; D012475:Salmonella / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013045:Species Specificity; D013481:Superoxides / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D004731:Endotoxins; D008050:Lipid A; D008070:Lipopolysaccharides; D013481:Superoxides; D015544:Inositol 1,4,5-Trisphosphate