Platelet-activating factor is a mediator in tumor necrosis factor/galactosamine-induced lethality.
We here report that administration to mice of WEB2170, a potent platelet-activating factor (PAF) receptor antagonist, prevents both PAF-induced and murine tumor necrosis factor (TNF)-induced lethality in galactosamine (GalN)-sensitized mice. Furthermore, we demonstrate that pretreatment with alpha 1-acid glycoprotein (AGP) or interleukin-1 (IL-1) protects against TNF-induced, but not against PAF-induced lethality. We conclude that PAF is a mediator in TNF/GalN-induced lethal shock, but that the protection conferred by AGP or IL-1 pretreatment is not at the level of scavenging PAF.
Libert
C
C
Laboratory of Molecular Biology, University of Ghent, Belgium.
Van Molle
W
W
Brouckaert
P
P
Fiers
W
W
D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D005260:Female; D005688:Galactosamine / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009961:Orosomucoid / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology* / Q000633:toxicity; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D012769:Shock / Q000503:physiopathology; D014230:Triazoles / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000502:physiology / Q000633:toxicity*
D001381:Azepines; D007375:Interleukin-1; D009961:Orosomucoid; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D014230:Triazoles; D014409:Tumor Necrosis Factor-alpha; D005688:Galactosamine; C063964:bepafant