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 (Mφ) were isolated 4 days later. Meφ from injured mice produced significantly greater amounts of reactive nitrogen intermediates and tumor necrosis factor-α in response to lipopolysaccharide and lipid A. Pertussis toxin (PTX) treatment of Mφ dose-dependently inhibited reactive nitrogen intermediate production in Mφ from sham-treated mice; however, Mφ from injured mice were insensitive to PTX-mediated inhibition. Conversely, tumor necrosis factor-α production was enhanced by PTX treatment, with Mφ from injured mice being more sensitive than Mφ from sham-treated mice to this effect of PTX. These results indicate that thermal injury increases Mφ 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 Mφ activity after thermal injury.