Characterization of leukotriene production in vivo and in vitro in resident and elicited peritoneal macrophages in chickens and mice

Abstract

Previously, we reported differences in arachidonic acid metabolism in elicited chicken peritoneal macrophages when compared with murine resident and elicited peritoneal macrophages. 1 We now describe leukotriene (LT) production in the same systems, using resident (murine) and inflammatory macrophages (from both species). Inflammatory (4- or 42-h Sephadex-elicited) peritoneal macrophages from chickens lacked the capacity to produce LT in vivo (following opsonized zymosan [OZ] stimulation) or in vitro, in response to A23187. In addition, chicken macrophages were unable to metabolize exogenously added LTC 4 or LTD 4 in vitro. In contrast, resident murine peritoneal macrophages produced measurable quantities of LTs (in vivo) within 5 min with an 8-fold increase after 45 min. LTC 4 was effectively converted to LTE 4 in vivo in a time-dependent manner (65% LTC 4/35% LTE 4 after 5 min stimulation with OZ and 6% LTC 4/94% LTE 4 after 60 min stimulation), but not in vitro. The lack of LTC 4 metabolism to LTE 4 in vitro could not be explained by cell-cell interaction between adherent and nonadherent cells. LTD 4 was not detected under any experimental condition. Murine peritoneal cells incubated with LTD 4 (with or without agonist) produced LTE 4 in a time-dependent fashion. Addition of l-cysteine (a dipeptidase inhibitor) did not explain the lack of detectable levels of LTD 4 following intraperitoneal stimulation with OZ. These results suggest that elicited chicken peritoneal macrophages are incapable of producing LTs compared to murine peritoneal macrophages. In addition, these studies fail to explain the different product profiles associated with in vivo stimulation of murine peritoneal macrophages as compared to in vitro stimulation.