M A West1, M H Li, S C Seatter, M P Bubrick. 1. Department of Surgery, Hennepin County Medical Center, University of Minnesota, Minneapolis 55415.
Abstract
UNLABELLED: Shock states with resulting inadequate cellular oxygen delivery may contribute to macrophage (M phi) activation or dysregulation. In this study we compared the effects of transient anoxia and endotoxin pretreatment (LPS1) on M phi mediator release with a second endotoxin stimulus (LPS2). METHODS: In vitro cultures of murine peritoneal exudate M phi were exposed to 2 hours of hypoxic or normoxic conditions, then incubated 22 hours under identical normoxic conditions +/- 10 ng/mL of LPS1 pretreatment. During the final 24 hours all M phis were exposed to a range of LPS2 concentrations. The M phi supernatants were assayed for tumor necrosis factor (TNF), interleukin 1 (IL-1), interleukin 6 (IL-6), prostaglandin E2 (PGE2), nitric oxide (NO), and superoxide release. RESULTS: LPS1 markedly inhibited M phi TNF release by LPS2, but hypoxia had no effect on LPS2-triggered TNF release. Hypoxia increased M phi IL-6 production in the absence of LPS1, but inhibited the LPS1 augmentation seen under normoxic conditions. Pretreatment with LPS1 increased NO production from LPS2 under normoxic conditions, but hypoxia inhibited this effect. Superoxide production increased by LPS1 under normoxic conditions, but hypoxia significantly inhibited superoxide release. CONCLUSIONS: The effects of transient anoxic exposure on LPS2-triggered M phi function are markedly different from the effects of pretreatment with septic stimuli (LPS1).
UNLABELLED: Shock states with resulting inadequate cellular oxygen delivery may contribute to macrophage (M phi) activation or dysregulation. In this study we compared the effects of transient anoxia and endotoxin pretreatment (LPS1) on M phi mediator release with a second endotoxin stimulus (LPS2). METHODS: In vitro cultures of murine peritoneal exudate M phi were exposed to 2 hours of hypoxic or normoxic conditions, then incubated 22 hours under identical normoxic conditions +/- 10 ng/mL of LPS1 pretreatment. During the final 24 hours all M phis were exposed to a range of LPS2 concentrations. The M phi supernatants were assayed for tumor necrosis factor (TNF), interleukin 1 (IL-1), interleukin 6 (IL-6), prostaglandin E2 (PGE2), nitric oxide (NO), and superoxide release. RESULTS: LPS1 markedly inhibited M phi TNF release by LPS2, but hypoxia had no effect on LPS2-triggered TNF release. Hypoxia increased M phi IL-6 production in the absence of LPS1, but inhibited the LPS1 augmentation seen under normoxic conditions. Pretreatment with LPS1 increased NO production from LPS2 under normoxic conditions, but hypoxia inhibited this effect. Superoxide production increased by LPS1 under normoxic conditions, but hypoxia significantly inhibited superoxide release. CONCLUSIONS: The effects of transient anoxic exposure on LPS2-triggered M phi function are markedly different from the effects of pretreatment with septic stimuli (LPS1).