THE MAST CELLS 



begin to swell and metachromatic material can now be seen to diffuse from 

 the granules into the cytoplasm and, ultimately, through the cell wall to form 

 a pericellular metachromatic halo. The exceedingly thin cell wall may rupture, 

 leaving behind only a few swollen and usually basophilic granules and a nucleus 

 now also swollen and stained. These findings were, in fact, known to Ehrlich 

 (1878), as we can very well appreciate now that his own thesis is available for 

 consultation (1956). Ehrlich believed the nuclear staining to be due to the 

 formation of a double salt. It seems likely that the heparin penetrates the 

 nucleus of a dead cell and there combines with its basic protein, forming a 

 stainable complex (Figs. 47-50). Sometimes the diffuse pericellular meta- 

 chromasia can be seen to concentrate around, and become attached to, adjacent 

 connective tissue fibrils (Riley, 1954, 1956, p. 400; and see Figs. 47 and 48). 



However, if the dye is applied to the mast cell, not in water but in normal 

 saline or Ringer-Locke solution, the granules stain successively as before but 

 now appear to be preserved rather than destroyed by the dye. Following this 

 lead, I tested the effects of adding the dye toluidine blue to an intraperitoneal 

 injection of saline in the rat. To all outward appearances the mast cells and 

 their granules seemed well preserved when fresh tissue spreads were examined 

 at the end of the experiments. There was neither degranulation nor disruption. 

 Yet, as in Fawcett's experiment, histamine had been released into the surround- 

 ing fluid. Presumably one amine (the dye) had replaced the other (histamine). 

 This process may perhaps occur under yet more physiological circumstances: 

 thus Feldberg and Smith (1953) showed that tryptamine and 5-hydroxy- 

 tryptamine can act as histamine-liberators in vivo. One might speculate that 

 the traces of 5-HT which are normally found in the mast cells of the mouse 

 and rat (Benditt et al, 1955; West and Parratt, 1957) have reached the cells 

 in this way. 



The above findings thus draw attention to the complexity of the mast-cell 

 granule. Heparin, in common with other electro-negative colloids, can be 

 stored as droplets in cells of the reticuloendothelial system (Asplund et ai 

 1939); but these are not mast cells (Isidor, 1954). The granules in young mast 

 cells in the rat tend to be basophilic with toluidine blue and stain positively 

 with the periodic acid-Schiff method (Jorpes et al, 1948), whereas the more 

 mature granule is metachromatic and PAS-negative (Riley, 1953a). Mast cells 

 also rapidly incorporate and store labelled sulphate (Jorpes et al, 1953). These 

 findings certainly suggest that at least a final rearrangement and sulphation 

 of the heparin molecule occurs inside the mast cell. Somewhat similar con- 

 siderations apply to the histamine and 5-hydroxytryptamine in mast cells. 

 Thus, Schayer (1956) has shown that a suspension of rat mast cells can take up 

 labelled histidine from the medium and convert it into labelled histamine. 

 According to Lagunoff et al (1957) and Hagen and Lee (1958) the mast cells 



124 



