Oxatomide protects against degranulation of rat peritoneal mast cells during in vitro challenge with antigen or...

The ultrastructure of isolated rat peritoneal mast cells was evaluated after in vitro degranulation and treatment with oxatomide, a new anti-allergic compound. In a first series of experiments, mast cells of rats infected with Trichinella spiralis larvae were incubated with Trichinella larvae somatic antigen to produce histamine release. The release was visualized in the electron microscope by exocytosis of the peripheral amine-containing granules, which resulted from fusion between several perigranular membranes and fusion of these membranes with the plasma membrane. A more drastic degranulation was provoked in a second series by incubation of unsensitized mast cells in the presence of the amine liberator compound 48/80. This treatment led to a complete extrusion of the granules in most of the cells, while in a smaller number of cells, only large vacuoles containing remnants of several granules were seen. The plasma membrane of these cells however was intact and there were no signs of exocytosis. The effect of oxatomide against mast cell degranulation was dose-dependent and comparable for the two types of histamine release. After incubation with high doses (10(-4) M, 5.10(-5) M) granule liberation was rarely observed in antigen-challenged and compound 48/80-challenged cells. Protection was apparently situated at the level of the plasma membrane which seemed to be unable to fuse with the perigranular membranes while fusion of perigranular membranes of individual granules was still possible. None of the tested concentrations of oxatomide induced spontaneous degranulation. High doses, however, led in a number of cells to some ultrastructural alterations such as partial disappearance of plasmalemmal folds, slight cytoplasmic oedema and the appearance of intranuclear microtubules. The latter were also seen in oxatomide-treated challenged mast cells.