Activation of bone marrow-derived macrophages by repeated zymosan phagocytosis leads to enhanced prostaglandin synthesis.

Bone marrow-derived macrophages were stimulated by the addition of zymosan. Phagocytic activity and prostaglandin release were taken as a measure of the activation state of the macrophages. Repeated stimulation with zymosan of macrophages which had been freed from extracellular zymosan led to further phagocytosis and prostaglandin formation. Very low amounts of prostaglandins were synthesized after the second phagocytic stimulus if the time interval between the first and second stimulation was one or two hours. In contrast, however, if the second phagocytic stimulation occurred 9 hours after the first stimulation there was a doubling of the number of phagocytosed zymosan particles and a fifteen fold increase in prostaglandin synthesis. These findings are explained as the consequences of internalized membrane material which provides additional substrates for the generation of prostaglandins.