THE MAST CELLS 



the granules had previously been supravitally stained with toluidine blue, the 

 diamidine rapidly discharged the metachromatic dye from the granules, leaving 

 the nuclei of nearby fibrocytes and mesothelial cells still stained. Thereafter 

 the mast cells slowly broke up into a mass of debris, but in general this dis- 

 ruption was neither so rapid nor so clearly accompanied by vacuolation as it 

 had been in tissue spreads prepared from rats which had received the same 

 liberators through the blood stream. 



With anaphylatoxic serum well-marked vacuoles appeared in the peripheral 

 cytoplasm of the mast cells accompanied by disappearance of granules, whereas 

 with normal rat serum the granules persisted for at least half an hour. 

 Although it is clear that direct action does occur in vitro, the mast-cell response 

 was less pronounced than when the histamine-liberators or the anaphylatoxic 

 serum reached the mast cells through an intact circulation. 



Discussion 



The reasons for the present investigation have already been outlined. 

 Briefly it may be recalled that in shock states in the dog histamine and heparin 

 are released simultaneously from the liver, the heparin being thought to come 

 from tissue mast cells. It was of interest, therefore, to investigate the relation 

 of mast cells to histamine in an animal such as the rat, where the mast cells 

 can be readily observed in tissue spreads. 



Chemical histamine-liberators 



All the histamine-liberators tested were found to produce, on intravenous 

 injection in the rat, obvious damage to tissue mast cells and particularly to 

 those peritoneal mast cells, filled with discrete, metachromatic granules, which 

 lie near capillaries or free in the tissue spaces (type-II cells). However, inter- 

 pretation of this apparently straightforward effect is complicated by the finding 

 that any tissue oedema, including that produced by the injection of histamine 

 itself, leads to disruption of the mast cells in the area. We have, therefore, to 

 distinguish between a primary action of the liberators directly on mast cells 

 and the indirect or secondary degranulation of mast cells mediated through 

 the oedema that follows histamine release. 



Direct action on mast cells 



Direct action of the histamine-liberators on the mast cells is certainly 

 suggested by the following observations. First, the rapidly acting and potent 

 histamine-liberators, stilbamidine and 2-hydroxy stilbamidine, can be seen, 

 in virtue of their fluorescence in ultra-violet light, to be concentrated within 



68 



