ERYTHROCYTES INCREASE LEUKOTRIENE C-4 RELEASE FROM HUMAN EOSINOPHILS - CHARACTERIZATION AND EXAMINATION OF POSSIBLE MECHANISMS

There has been considerable interest in the role of eosinophils in the pathogenesis of asthma and allergic diseases. While examining the con ditions necessary for the release of leukotriene C-4 (LTC(4)) from hum an eosinophils activated by immunoglobulin G-Sepharose (IgG-Seph), we observed that red blood cells (RBCs) potentiated eosinophil LTC(4) rel ease. The time course of IgG-Seph-stimulated LTC(4) release was prolon ged in the presence of RBCs. After 45 min of incubation, eosinophils w ithout RBCs released 0.95 +/- 0.11 ng/10(6) cells, and those with RBCs released 3.69 +/- 0.67 ng/10(6) cells. Control experiments indicated that the effect was not due to platelet contamination of the RBCs and could not be reproduced with RBC supernatants or RBC membrane ghosts. An interesting characteristic of this interaction was that the eosinop hils and RBCs had to be in close contact for the enhancement to occur. We also observed that at low calcium concentrations (0.6 mM), the eos inophils had to be primed with fMLP for the RBC effect to occur, but p riming was not required at higher calcium concentrations. Several poss ible mechanisms that would explain the RBC effect on eosinophil LTC(4) release were examined: (1) RBCs block the metabolism of LTC(4); (2) R BCs protect the eosinophils from oxidative damage; (3) RBCs provide a substrate (or enzyme) that allows increased eosinophil LTC(4) producti on. These mechanisms failed to explain our observation that erythrocyt es enhance eosinophil LTC(4) release, however, suggesting that alterna tive mechanisms are responsible for this effect.