Zymosan enhances leukotriene D4 metabolism by porcine alveolar macrophages.

Porcine alveolar macrophages (AM) metabolize leukotriene D4 (LTD4) to leukotriene E4 (LTE4). In the present study, the ability of a fluid-phase AM stimulus (A23187) and a phagocytic stimulus (opsonized zymosan) to augment LTD4 metabolism was examined. Both stimuli increased the release of superoxide (O-2) anions. However, whereas zymosan caused a consistent reduction in surface free energy, the effect of A23187 was variable. Similarly, zymosan induced release of the lysosomal enzymes N-acetyl-beta-D-glucosaminidase and arylsulphatase (mean net release, 14.9% and 12.0%, respectively), whereas release induced by A23187 was smaller (mean net release 1.42% and 1.31%, respectively) and of marginal statistical significance. Zymosan, but not A23187, caused a significant (P less than 0.005) augmentation of LTD4 inactivation: from 93 +/- 7 pM/10(7) cells (69 +/- 5% of added LTD4) at 60 min by control AM, to 117 +/- 3 pM/10(7) cells (88 +/- 2% of added LTD4) at 60 min by zymosan-treated AM. Zymosan also induced the release of LTD4 inactivating capacity (128 +/- 21 pM LTD4/10(7) AM/60 min) into the supernatant. Conversion of LTD4 to LTE4 by zymosan-treated AM and their supernatants was confirmed chromatographically. In addition, LTD4 inactivation by AM and their supernatants was inhibited by 10 mM L-cysteine. These data suggest that zymosan released a dipeptidase, possibly of lysosomal origin, which catalysed the conversion of LTD4 to LTE4.