Prostaglandin synthesis by macrophages requires a specific receptor-ligand interaction.

Abstract

The ingestion of particles by mouse macrophages leads to the prompt induction of prostaglandin (PG) synthesis. The endocytic process was dissected and the requirements of PGE synthesis for particle attachment, membrane interiorization and phagosome-lysosome fusion were examined. Macrophages that were loaded with the polyanion dextran sulfate and exhibited a greater than 99% inhibition of phagosome-lysosome fusion produced normal amounts of PGE upon challenge with zymosan. Inhibition of membrane interiorization with cytochalasin D was similarly ineffective in blocking PGE synthesis. The addition of large numbers of unmodified polystyrene latex beads, which were rapidly ingested by macrophages, failed to stimulate PGE synthesis. When macrophages were challenged with latex beads coated with immune complexes, an increased synthesis of PGE resulted. No response occurred if the complex was prepared with the F(ab'')2 fragment of immunoglobulin G. Similar results occurred when nonphagocytizable Sephadex beads coated with immune complexes were employed. Particle binding to the Fc receptor of the macrophage plasma membrane apparently is a sufficient stimulus for PGE synthesis.