THERMAL-INJURY INDUCES MACROPHAGE HYPERACTIVITY THROUGH PERTUSSIS-TOXIN-SENSITIVE AND PERTUSSIS-TOXIN-INSENSITIVE PATHWAYS

C57BL/G mice were subjected to a full thickness scald thermal injury c overing 25% of their total body surface area, and thioglycollate elici ted peritoneal macrophages (M phi) were isolated 4 days later. M phi f rom injured mice produced significantly greater amounts of reactive ni trogen intermediates and tumor necrosis factor-alpha in response to li popolysaccharide 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 fa ctor-alpha production was enhanced by PTX treatment, with M phi from i njured mice being more sensitive than M phi from sham-treated mice to this effect of PTX, These results indicate that thermal injury increas es M phi sensitivity to lipopolysaccharide by a mechanism that is both PTX sensitive and PTX insensitive, thereby suggesting a role for G pr oteins in the modulation of M phi activity after thermal injury.