Metabolism of leukotriene D4 by porcine alveolar macrophages.

Porcine alveolar macrophages (AM), as we reported in 1981, inactivate slow-reacting substance of anaphylaxis (SRS-A) in a time- and cell-number-dependent fashion. In the present study, metabolism of synthetic leukotriene D4 (LTD4) to leukotriene E4 (LTE4) by AM was demonstrated (mean conversion, 216 pmoles LTD/10(7) AM/60 min). The metabolism was inhibited by cooling or by removal of calcium ions plus addition of EDTA but not by dinitrophenol or puromycin, lipoxygenase inhibitors, the peroxidase inhibitor aminotriazole, or the hydroxyl ion scavenger benzoic acid. Similarly, although the addition of catalase plus superoxide dismutase significantly augmented (169 +/- 25% control) SRS release from dispersed porcine lung cells, the presence of these enzymes did not prevent LTD4 metabolism by AM. Inhibitors of gamma-glutamyl transpeptidase were also without effect but the dipeptidase inhibitors L-cysteine and dithiothreitol significantly reduced the conversion, as did pretreatment of AM with thermolysin (100 micrograms/ml). These data indicate that an AM dipeptidase, which may at least partly be located on the cell surface, converts LTD4 to the less bioactive LTE4.