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Electron microscope studies on the release of histamine from rat peritoneal mast cells.

The effects of some histamine-liberating agents on rat peritoneal mast cells were examined under the electron microscope and the release of histamine was measured by means of bioassay.Compound 48/80, when given in a small dose (0.1μg/ml), caused swelling of the granules and widening of the perigranular space only in a small part of the cells. With moderate doses (1.0-5.0μg/ml), perigranular vacuoles developed either individually causing a honeycomb-like cytoplasm or, by confluence, into a single large vacuole leaving a thin cytoplasmic sheet at the periphery of the cell. Degranulation occurred mainly in the cells with the former type of vacuolation. When a very large dose (100μg/ml) of compound 48/80 was given, vacuolation was marked but the granules were neither discharged nor swollen. Toluidine blue (50μg/ml) and sinomenine (500μg/ml) caused cytological changes in the mast cells similar to those under moderate dose treatment with compound 48/80. The effect of anti-rat rabbit serum was characterized by greater swelling of the granules and more conspicuous peripheral vacuolation than in the cases of the histamine liberators. Pretreatment with 10-4M of 2, 4-dinitrophenol almost completely inhibited any cytological change inducible by compound 48/80.By comparing the electron micrographs with the grades of histamine release in the corresponding cases measured by bioassay (Table 1), it was proposed that the most reliable morphological criterion of the release of histamine is neither degranulation nor granule swelling, but the occurrence of vacuoles around the granules.