Rabbit lymphocyte factors modulate prostaglandin biosynthesis in alveolar macrophages

We have previously shown that alveolar macrophages from BCG-infected rabbits release less prostaglandins (PG) and arachidonic acid than normal resident macrophages. In order to investigate the possible role of lymphocytes in modulating PG secretory activity of macrophages, we added the supernatant of spleen lymphocyte culture to alveolar macrophages prelabelled with [14C] arachidonic acid, and subsequently quantitated the release of PGs and arachidonic acid by macrophages. It was found that lymphocytes stimulated by phytohaemagglutinin (PHA) released soluble factors which inhibited arachidonic acid release and PG synthesis by macrophages. This inhibition was not seen with either supernatant of lymphocytes cultured without PHA, or when PHA was added at the end of lymphocyte incubation. The inhibitor factors were pronase-sensitive and exhibited molecular weight heterogeneity. Production of these could be enhanced by indomethacin treatment. These lymphokines might play a regulatory role in the suppression of macrophage PG synthesis in cell-mediated immunity.