Sequential Exocytosis of Storage Granules during Antigen‐Induced Histamine Release from Sensitized Rat Mast Cells in vitro An electron microscopic study

The morphological changes appearing in sensitized rat mast cells incubated with antigen at 25° C for times ranging from 30 s to 10 min were studied using light and electron microscopy. Histamine release was assayed in parallel. After a latent period of 30 s, during which no histamine release or morphological changes occurred, degranulation and histamine release commenced and increased progressively with time. The first changes were seen in the most peripherally‐located granules, and consisted of a fusion of the cell membrane with the perigranular membrane and a swelling and a reduction of the electron‐density of the granules. With increasing time these changes were seen to spread deeper into the cells, resulting in the formation of labyrinthic cavities contatining changed granules; such granules were also seen outside the cells. Using the extracellular tracer lanthanum these apparently intracellular cavities were demonstrated to be in unbroken communication with the extracellular milieu. Thus when sensitized rat mast cells are incubated with antigen sequential exocytosis of histamine‐storing granules take place. The results agree with the hypothesis that histamine release takes place by ion exchange between histamine and extracellular cations both in granules expelled from the cells and in those retained in cavities open to the exterior.