Thermal injury induces macrophage hyperactivity through pertussis toxin-sensitive and -insensitive pathways.
C57BL/6 mice were subjected to a full thickness scald thermal injury covering 25% of their total body surface area, and thioglycollate elicited peritoneal macrophages (Mphi were isolated 4 days later. Mphi from injured mice produced significantly greater amounts of reactive nitrogen intermediates and tumor necrosis factor-alpha in response to lipopolysaccharide and lipid A. Pertussis toxin (PTX) treatment of Mphi dose-dependently inhibited reactive nitrogen intermediate production in Mphi from sham-treated mice; however, Mphi from injured mice were insensitive to PTX-mediated inhibition. Conversely, tumor necrosis factor-alpha production was enhanced by PTX treatment, with Mphi from injured mice being more sensitive than Mphi from sham-treated mice to this effect of PTX. These results indicate that thermal injury increases Mphi sensitivity to lipopolysaccharide by a mechanism that is both PTX sensitive and PTX insensitive, thereby suggesting a role for G proteins in the modulation of Mphi activity after thermal injury.
Schwacha
M G
MG
Department of Surgery, Brown University School of Medicine and Rhode Island Hospital, Providence 02903, USA. mschwacha@lifespan.org
Somers
S D
SD
D000818:Animals; D002056:Burns / Q000276:immunology*; D007700:Kinetics; D008050:Lipid A / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009589:Nitrogen Oxides / Q000378:metabolism*; D037342:Pertussis Toxin; D012016:Reference Values; D013864:Thioglycolates / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D008050:Lipid A; D008070:Lipopolysaccharides; D009589:Nitrogen Oxides; D013864:Thioglycolates; D014409:Tumor Necrosis Factor-alpha; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin