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 l eukotrienes (LTs) and lipoxins (LXs) was affected by the expression of defi nite levels of macrophage activation. We used a system of murine peritoneal macrophages at different states of activation consisting in resident macro phages and FCS-, thioglycollate- or Corynebacterium parvum-elicited macroph ages. The profile of lipoxygenase metabolites in resident macrophages was c haracterized 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 respons ive to the challenge with interferon gamma pills LPS, as measured by the ge neration of NO and tumor necrosis factor alpha. Resident as well as FCS-eli cited macrophages also generated appreciable quantities of LXs (A(4) and B- 4). Thioglycollate-elicited macrophages, which expressed a state of 'respon sive' macrophages, showed a block of the LT and LX synthesis. This block wa s also present in C. parvum-elicited macrophages which expressed a fully 'a ctivated' phenotype, reflected by their capacity of releasing NO and tumor necrosis factor ex even though they were not challenged. These results prov ide the first evidence that the level of 'responsive' as well as 'activated ' macrophages was associated with of a simultaneous block of LTB4 and LXs. (C) 2000 Elsevier Science B.V. All rights reserved.