The diminished production of arachidonic acid oxygenation products by elicited mouse peritoneal macrophages: possible mechanisms.

Abstract

Abstract Resident and elicited populations of mononuclear phagocytes differ in their capacity to secrete various products relevant to immune and inflammatory responses. We compared the release of prostaglandins by elicited and resident macrophage populations. Resident populations of peritoneal macrophages were obtained from specific pathogen-free mice and elicited populations from mice that had received i.p. injections of thioglycollate broth, BCG, or CP. Macrophages obtained by enzymatic dispersion of 7-day-old-carrageenan granulomas were also studied. Resident macrophages release large amounts of PGE2 and 6-keto-PGF1α when challenged in culture with zymosan. Elicited and granuloma macrophages are far less responsive to zymosan as reflected by decreased release of PG. Resident macrophages give a 42-fold increase in PGE2 release when exposed for 4 hr to 50 jug/ml of zymosan compared with only a 5-fold increase in PGE2 release by thioglycollate-elicited macrophages exposed to 300 μg/ml. A similar loss of reactivity to zymosan in terms of PG release was found with macrophages from BCG- or CP-treated mice. Elicited and resident cells are also clearly differentiated by the activity of certain cell associated enzymes. Elicited cells from BCG, CP, thioglycollate, and carrageenan-treated mice showed decreased 5’-nucleotidase and elevated leucine aminopeptidase activities compared with resident cells. Some of the possible mechanisms accounting for these differences in PG production have been examined by examining several parameters that may regulate PG production. There are no indications that phagocytic capacity or the ability to release or sequester PG accounted for the differences observed. Measurement of lipid deacylation rates showed a marked decrease of the rates of arachidonic acid release from thioglycollate-elicited cells compared with resident cells.