EFFECTS OF HISTAMINE-LIBERATORS 



Group b. Slow injection. Following slow (30-60 sec.) injection of these 

 diamidines an entirely different picture is seen. Instead of the sharply defined 

 fluorescence of mast cells in the peritoneal tissues there are pools of pale grey 

 to gold fluorescent material around some of the vessels, with perhaps some 

 increase of fluorescence in the nearby fat. Counterstaining with toluidine 

 blue, as above, reveals that there is widespread disintegration of the mast cells, 

 and routine fixation and staining of spreads from these animals confirm the 

 disintegrating effect on the mast cells of the diamidines. Individual granules 

 are swollen and stain poorly, and are often scattered. In addition some cells 

 show vacuolation. This is best seen after 2-hydroxy stilbamidine. Here 

 many of the type-II mast cells in the peritoneal spreads show the presence of 

 intracytoplasmic vacuoles, whereas nearby type-I cells may remain unchanged 

 (Fig. 21). As the injection time, and hence the survival time, of the experi- 

 mental animal is increased, it can be seen that this vacuolation progresses until 

 many of the cells entirely disappear or leave behind only a few granules sur- 

 rounded by a wisp of frothy cytoplasm. In areas where these changes in mast 

 cells are prominent the small blood vessels are dilated and the connective tissue 

 appears oedematous. 



In animals which have survived for more than a few minutes, extensive 

 areas of vasodilatation and oedema are present, and in such regions the mast- 

 cell granules gradually lose their ability to take on the basic stain ("degranula- 

 tion"). Some of the degranulated cells are swollen; others show in addition 

 a characteristic punctate appearance in which a few granules appear to have 

 escaped lysis and stand out in sharp contrast to the pale cytoplasm. Where 

 the oedema is maximal no trace of the former mast-cell population of the tissue 

 may remain. 



Non-fluorescent histamine-liberators 



The changes produced in the mast cells by the non-fluorescent histamine- 

 liberators (table) as seen in stained spreads are very similar to those described 

 above. 



Propamidine and Pentamidine give rise to occasional vacuolation and 

 widespread degranulation in peritoneal mast cells as does the 10-carbon 

 aliphatic diamine, and there is also some degranulation in the mast cells of the 

 subcutis. The 7-carbon diamine, which is less active as a histamine-liberator 

 than the 10-carbon compound (Macintosh and Paton, 1949), is also less potent 

 in its effect on mast cells. 



The injection of Witte's peptone produces similar degranulating and 

 disintegrating effects on the mast cells of the rat, despite the fact that in this 

 species peptone does not give rise to the dramatic shock seen in the dog. 



63 



