EFFECTS OF HISTAMINE-LIBER ATORS 



the peritoneal mast cells prior to their disruption. Second, the fluorescent 

 histamine-liberators, when applied to fresh spreads of peritoneum from 

 intravitally stained animals, rapidly discharge the dye from the granules, after 

 which the mast cells disintegrate. Third, all the histamine-liberators so far 

 tested, whether fluorescent or not, lead to the appearance of curious intra- 

 cytoplasmic vacuoles, and with 2-hydroxy stilbamidine vacuolation may be 

 extreme. In contrast to this, swelling and degranulation of mast cells are 

 unaccompanied by vacuolation when brought about by (a) local oedema, 

 histamine-induced or otherwise, or (b) the addition of aqueous solutions to 

 mast cells in fresh tissue spreads. It is evident, therefore, that the histamine- 

 liberators have a definite effect on both cytoplasm and granules of the mast 

 cell. 



The concentration of the chemical liberators within the mast cells may well 

 depend on the fact that the basic diamidines precipitate heparin from solution 

 (Macintosh and Paton), and one may recall here that the dye, toluidine blue, 

 can be similarly used for the quantitative titration of heparin. But with the 

 chemical histamine-liberators the process does not stop there; disintegration 

 of the mast cell follows. Thus the diamidines act on mast cells in a different 

 way from a basic dye such as toluidine blue, which, if anything, preserves 

 rather than destroys the granules which have taken up the dye. If, therefore, 

 as Macintosh and Paton suggest, chemical histamine-liberators act by displacing 

 histamine from its natural depots in the tissues, the present evidence suggests 

 that these depots are the tissue mast cells. 



Effect of anaphylatoxin on mast cells 



Agar-activated anaphylatoxin, prepared as described above, is a known 

 histamine-liberator (Rocha e Silva) and in the present experiments its visible 

 action on mast cells proved similar to that of the chemical liberators, even to 

 the appearance of vacuolation in the cells during their disruption. Ana- 

 phylatoxin has also the same power of acting topically when applied directly 

 to mast cells in fresh tissue spreads. Thus we have two apparently different 

 types of substance capable of releasing histamine, both of which produce very 

 similar changes in mast cells. It therefore seems probable that these changes 

 in the mast cells are significantly related to the liberation of histamine. 



We now know that these changes do, in fact, occur in true anaphylaxis 

 (Stuart, 1952). The earlier observations of Jaques and Waters (1941) on the 

 degranulation and disruption of mast cells in the liver of the shocked dog have 

 been confirmed for mast cells in the tissues of the hamster (Wegelius et al, 

 19556), guinea pig (Mota and Vugman, 1956), mouse (Carter et al, 1957) and 

 rat (Keller, 1957). This further strengthens the view that the findings in 

 the experiments described above are relevant not only to the study of the 



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