CHARACTERIZATION OF LEUKOTRIENE PRODUCTION IN-VIVO AND IN-VITRO IN RESIDENT AND ELICITED PERITONEAL-MACROPHAGES IN CHICKENS AND MICE

Previously, we reported differences in arachidonic acid metabolism in elicited chicken peritoneal macrophages when compared with murine resi dent and elicited peritoneal macrophages.(1) We now describe leukotrie ne (LT) production in the same systems, using resident (murine) and in flammatory macrophages (from both species). Inflammatory (4- or 42-h S ephadex-elicited) peritoneal macrophages from chickens lacked the capa city to produce LT in vivo (following opsonized zymosan [OZ] stimulati on) or in vitro, in response to A23187. In addition, chicken macrophag es were unable to metabolize exogenously added LTC(4) or LTD(4) in vit ro. In contrast, resident murine peritoneal macrophages produced measu rable 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 ce lls. LTD(4) was not detected under any experimental condition. Murine peritoneal cells incubated with LTD(4) (with or without agonist) produ ced LTE(4) in a time-dependent fashion. Addition of L-cysteine (a dipe ptidase inhibitor) did not explain the lack of detectable levels of LT D(4) following intraperitoneal stimulation with OZ. These results sugg est that elicited chicken peritoneal macrophages are incapable of prod ucing LTs compared to murine peritoneal macrophages. In addition, thes e studies fail to explain the different product profiles associated wi th in vivo stimulation of murine peritoneal macrophages as compared to in vitro stimulation.