Thermal injury induces macrophage hyperactivity through pertussis toxin-sensitive and -insensitive pathways

C57BL/G mice were subjected to a full thickness scald thermal injury covering 25% of their total body surface area, and thioglycollate elicited peritoneal macrophages (M phi) were isolated 4 days later. M phi 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 M phi dose-dependently inhibited reactive nitrogen intermediate production in M phi from sham-treated mice; however, M phi from injured mice were insensitive to PTX-mediated inhibition. Conversely, tumor necrosis factor-alpha production was enhanced by PTX treatment, with M phi from injured mice being more sensitive than M phi from sham-treated mice to this effect of PTX, These results indicate that thermal injury increases M phi 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 M phi activity after thermal injury.