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

The occurrence of histamine in the granules of mammalian mast cells has been established by combined bioassay and histological studies (RILEY and WEST, 1953), by chemical analysis of the granule fraction (HAGEN, BARRNETT and LEE, 1959) and further by fluorescence histochemistry for histamine (JUHLIN and SHELLEY, 1966; YAMASAKI, 1967; TAKAYA, 1969). Certain substances such as compound 48/80 (PATON, 1951; FAWCETT, 1954), Sinomenine (MAYEDA, 1953; YAMASAKI et al., 1955), toluidine blue (GAMBLE, 1952; SMITH, 1958 a) and anti-serum (KELLER and SCHWARZ, 1961; SAEKI, 1964) have been known to cause the release of histamine from mast cells with accompanying morphological changes in these cells such as degranulation and vacuolation. A large number of works have been directed to the morphological studies with special interest in the nature of cytological alterations in mast cells since these changes seemed to be an essential feature of the processes causally involved in the mechanisms of histamine release. As for the electron microscopic studies on the mast cell reactions to histamine liberators, there have been observations using compound 48/80 and other basic materials (SMITH and LEWIS, 1957; BLOOM, LARSSON and SMITH, 1957; HORSFIELD, 1965; BLOOM and HAEGERMARK, 1965; SINGLETON and CLARK, 1965). However, these studies seem to have not yet fully established the morphological criteria of the release of histamine. Some authors have regarded degranulation as the essential morphological manifestation of histamine liberation (FAWCETT, 1954; RILEY and WEST, 1955; UVNAS, 1964), while others thought much of either vacuolation (BLOOM, LARSSON and SMITH, 1957; SMITH and LEWIS, 1957) or alteration in the granule structure (BLOOM and HAEGERMARK, 1965). Further, as to how the histamine-liberating agents act on the cell parts, be it the cell membrane, cytoplasm, or granule itself, remains quite unknown. In the present investigation the effects of compound 48/80, sinomenine, toluidine blue and rabbit anti-rat serum on the mast cells in the rat peritoneal fluid were examined under the electron microscope. Special reference was made to the correlation between the morphological changes and the degree of histamine release from mast cells in order to find out whether extracellular discharge of granules is really essential for the histamine release induced by these histamine-liberating agents. The effect of the inhibitor of histamine release, 2, 4-dinitrophenol, was also examined morphologically.