Two distinct signal transduction pathways for the activation of guinea-pig macrophages and neutrophils by endotoxin.
Lipopolysaccharide (LPS, endotoxin) is a major component of the outer membrane of gram-negative bacteria. Although it interacts with many types of cells and is linked to numerous events associated with sepsis and endotoxic shock, the mechanisms underlying these actions are poorly understood. We found that Ca-signaling induced by endotoxin in guinea-pig neutrophils and macrophages is caused by cross-recognition of LPS with platelet activating factor (PAF) receptors. However, the synthesis of tumor necrosis factor-alpha or the priming effect of O2- production was not affected by PAF antagonists. Thus, at least two distinct pathways are involved in the actions of LPS, one via the PAF receptor, while the other is independent of a PAF receptor and Ca-signaling.
Waga
I
I
Department of Biochemistry, Faculty of Medicine, University of Tokyo, Japan.
Nakamura
M
M
Honda
Z
Z
Ferby
I
I
Toyoshima
S
S
Ishiguro
S
S
Shimizu
T
T
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D018118:Chloride Channels / Q000187:drug effects / Q000502:physiology; D003001:Cloning, Molecular; D004731:Endotoxins / Q000633:toxicity*; D004926:Escherichia coli; D005260:Female; D006168:Guinea Pigs; D007739:L Cells; D008050:Lipid A / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008262:Macrophage Activation / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D009865:Oocytes / Q000187:drug effects / Q000502:physiology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis; D014982:Xenopus laevis
D001381:Azepines; D018118:Chloride Channels; D004731:Endotoxins; D008050:Lipid A; D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D011994:Recombinant Proteins; D014230:Triazoles; D014409:Tumor Necrosis Factor-alpha; C039351:platelet activating factor receptor; D013481:Superoxides; C068035:4-(2-chlorophenyl)-2-(2-(4-isobutylphenyl)ethyl)-6,9-dimethyl-6H-thieno(3,2-f)(1,2,4)triazolo(4,3-a)(1,4)diazepine; D002118:Calcium