Ultrastructural changes in mouse peritoneal mast cells in response to L-leucine methyl ester or anti-IgE.

We studied the ultrastructural features of mouse peritoneal mast cells in response to a non-immunologic lysosomotropic agent, L-leucine methyl ester (Leu-OMe), as compared to well-known immunologic stimulation mediated by anti-IgE antibodies. Total peritoneal exudate cells were collected from CBA/J mice, with mast cells representing 3 to 8% of total cells. The secretory granules in unstimulated mast cells were heterogeneous in size and shape, but intragranular material displayed a homogeneous electron-dense appearance. Stimulation with either Leu-OMe, for Leu-OMe doses lower than 1.5 mM, or anti-IgE was associated with fusion of the granule membranes with one another and with the plasma membrane, as evidenced by morphologic changes noted by electron microscopy. Ultrastructurally, electron density characterizing the granular matrix decreased to varying degrees in the granules, as did its homogeneity, even within a given mast cell. At higher Leu-OMe doses (> 1.5 mM), the effect of this lysosomotropic compound on mast cells was associated with an apparent loss of membrane and cellular integrity, suggesting high Leu-OMe dose-mediated cytotoxicity. These results show that activation induced in mouse peritoneal mast cells by Leu-OMe and anti-IgE may have distinct characteristics, as assessed by morphologically different patterns. Furthermore, high Leu-OMe doses (> 1.5 mM) induced cytotoxicity targeted toward mast cells.