Enhancement of leukotriene C4 release from primate airway macrophages by cellular interactions

1. Cells were obtained from the lungs of Macaque monkeys by bronchoalveolar lavage in order to study the role of cellular interactions in the release of leukotriene C4 (LTC4). 2. In normal monkeys, macrophages were the most abundant cell type recovered, whereas in monkeys sensitized with Ascaris suum there was an increase in the numbers of eosinophils and mast cells recovered. 3. Challenge of cells from both groups of animals with an optimal concentration of opsonized zymosan (OPZ) resulted in the time-dependent release of LTC4 from macrophages. However, release was significantly greater in cells obtained from sensitized donors compared to normal donors. 4. Density-gradient centrifugation of cells lavaged from sensitized donors was used to prepare fractions containing both eosinophils and mast cells. Addition of these cells to macrophage populations obtained from non-sensitized donors caused a significant enhancement of OPZ-induced LTC4 release. In the absence of macrophages no significant release of LTC4 was detected from eosinophil/mast cell-containing fractions stimulated with OPZ, despite the fact that the zymosan had been phagocytosed by the eosinophils. 5. There was a significant correlation between the percentage enhancement of LTC4 release and the number of eosinophils added. However, there was not a significant correlation with the number of mast cells added. 6. These results suggest that a cellular interaction between macrophages and eosinophils may be important in the regulation of mediator synthesis and release. The precise mechanism of this effect remains to be elucidated.