The effects of phagocytosis, dextran sulfate, and cell damage on PGE1 sensitivity and PGE1 production of macrophages.

During phagocytosis of zymosan or latex particles and after treatment with dextran sulfate, rat peritoneal macrophages responded to PGE 1 by an elevated and prolonged production of cyclic AMP. Levels of cyclic AMP were not only augmented at the maximal effective concentrations of PGE 1 but also at low, normally ineffective concentrations. Phagocytosis-induced enhancement of PGE 1 sensitivity was proportional to the amount of interiorized particles, was independent of opsonizing factors, and did not occur in lymphocytes. In contrast, phagocytosis of silica particles or treatment with carrageenan caused a rapid loss of the response to PGE 1 , which was followed later by cell damage. Synthesis and release of PGE 1 was induced in macrophages by phagocytosis of zymosan but not of latex particles. Zymosan-induced PGE 1 release was rather delayed and occurred at a high rate when the enhanced PGE 1 sensitivity during phagocytosis had returned to near normal. Exposure of macrophages to silica particles or carrageenan also caused a high release of PGE 1 , however, it was associated with progressive enzyme leakage, which was used as a criterion for cell damage. These observations suggest that phagocytosis-induced enhancement of PGE 1 sensitivity combined with a subsequent release of PGE 1 may be a sensitive control mechanism that may selectively regulate macrophage function under physiologic conditions. In contrast, the release of large amounts of PGE 1 when associated with a loss of PGE 1 sensitivity, may lead to an uncontrolled inflammatory response.