Relationship of prostaglandin secretion by rabbit alveolar macrophages to phagocytosis and lysosomal enzyme release

Abstract

The phospholipids of rabbit alveolar macrophages were pulse-labeled with [14C]-arachidonic acid, and the subsequent release of labeled prostaglandins [PG] was measured. Resting macrophages released measurable amounts of arachidonic acid, the PGE2, D2 and F2.alpha. and 6-oxo-PGF1.alpha.. Phagocytosis of zymosan increased the release of arachidonic acid and PG to 2.5 times the control value. In contrast, phagocytosis of inert latex particles had no effect on PG release. Indomethacin inhibited the release of PG, and, at high doses (20 .mu.g/ml), increased arachidonic acid release. Analysis of the cellular lipids showed that after zymosan stimulation the proportion of label was decreased in phosphatidylcholine, but not in other phospholipids or neutral lipids. Cytochalasin B, at a dose of 2 .mu.g/ml, inhibited the phagocytosis induced by zymosan but increased PG synthesis to 3.4 times the control. These data suggest that the stimulation of PG synthesis by zymosan is not dependent on phagocytosis. Exposure to zymosan also resulted in the release of the lysosomal enzyme, acid phosphatase. Cytochalasin B augmented the zymosan-stimulated release of acid phosphatase at the same dose that stimulated PG synthesis. Indomethacin, at a dose that completely inhibited PG synthesis, failed to block the lysosomal enzyme release. Thus despite some parallels between the release of PG and lysosomal enzymes, endogenous PG do not appear to mediate the release of lysosomal enzymes. The PG released from the macrophages may function as humoral substances affecting other cells.