The change in leukotrienes and lipoxins in activated mouse peritoneal macrophages

The aim of this study was to investigate to what extent the generation of leukotrienes (LTs) and lipoxins (LXs) was affected by the expression of definite levels of macrophage activation. We used a system of murine peritoneal macrophages at different states of activation consisting in resident macrophages and FCS-, thioglycollate- or Corynebacterium parvum-elicited macrophages. The profile of lipoxygenase metabolites in resident macrophages was characterized by the presence of high levels of 12-HETE, followed by 15-HETE, 5-HETE, LTB4 and 6-trans-LTB4, 6-trans-12-epi-LTB4. A comparable pattern was also found in FCS-elicited macrophages which appeared not to be responsive to the challenge with interferon γ plus LPS, as measured by the generation of NO and tumor necrosis factor α. Resident as well as FCS-elicited macrophages also generated appreciable quantities of LXs (A4 and B4). Thioglycollate-elicited macrophages, which expressed a state of ‘responsive’ macrophages, showed a block of the LT and LX synthesis. This block was also present in C. parvum-elicited macrophages which expressed a fully ‘activated’ phenotype, reflected by their capacity of releasing NO and tumor necrosis factor α even though they were not challenged. These results provide the first evidence that the level of ‘responsive’ as well as ‘activated’ macrophages was associated with of a simultaneous block of LTB4 and LXs.