title: Endotoxin-resistant mice are protected from PAF-induced bowel injury and death. Role of TNF, complement activation, and endogenous PAF production.
abstract: C3H/HeJ (endotoxin-resistant) mice have been used widely in biological research. However, the mechanism of endotoxin (LPS) resistance is only partially understood. In this study, we first investigated the differences in response to PAF, a mediator of endotoxin shock, between normal and C3H/HeJ mice. We found that in control mice, PAF (2.5 micrograms/kg) caused shock, hemoconcentration, complement activation, intestinal hypoperfusion, and necrosis with 75% mortality, whereas all C3H/HeJ mice survived, without complement activation or intestinal injury, and manifesting only mild hypotension and hemoconcentration. PAF also caused elevated serum TNF-alpha in some control mice but not in C3H/HeJ mice. We also observed that PAF induces endogenous PAF production and intestinal phospholipase A2 activation in normal mice, whereas PAF production and phospholipase A2 are suppressed in C3H/HeJ mice. The low endogenous PAF production may account, at least in part, for the resistance to LPS and PAF of C3H/HeJ mice.
authors.affiliation: Department of Pathology, Children's Memorial Hospital, Chicago, Illinois 60614.
authors.forename: X
authors.initials: X
authors.lastname: Sun
authors.forename: M S
authors.initials: MS
authors.lastname: Caplan
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: W
authors.initials: W
authors.lastname: Hsueh
mesh_terms: D000818:Animals; D003167:Complement Activation; D004731:Endotoxins / Q000633:toxicity*; D007421:Intestine, Small / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009336:Necrosis; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D010972:Platelet Activating Factor / Q000096:biosynthesis* / Q000633:toxicity*; D012772:Shock, Septic / Q000378:metabolism / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology*
chemical_list: D004731:Endotoxins; D010972:Platelet Activating Factor; D014409:Tumor Necrosis Factor-alpha; D010741:Phospholipases A; D054467:Phospholipases A2