THE MAST CELLS 



the type-I cells being relatively unaffected (Fig. 22). Many similar areas 

 could be found in the uterine fringes and omentum, along with the usual 

 vasodilatation and oedema in the surrounding connective tissue. The mast 

 cells in the subcutaneous connective tissue appeared normal. 



The changes in the mast cells after injection of anaphylatoxic serum thus 

 so closely resembled those seen after injection of the chemical histamine- 

 liberators that attempts were made to prepare an anaphylatoxin by incubating 

 rat serum with minimal amounts of the liberators in vitro. One ml. of saline 

 containing 0-5 mg. of stilbamidine or d-tubocurarine chloride was incubated 

 for two hours at 37° C. with 5 ml. of rat serum; 1-5 ml. of each of the final 

 products were thereafter slowly injected intravenously into each of three rats. 

 No shock was produced and there was no alteration in the appearance of the 

 mast cells in tissue spreads. However, since the possibility still remained that 

 the liberators might require leucocytes or platelets not present in serum for 

 their effects on mast cells, another set of sera was prepared by incubating 

 whole blood with the liberators before removing the serum. Again the results 

 were negative. 



Thus, although the final effects on mast cells of histamine-liberators and 

 agar-activated serotoxin are similar, it appears that their modes of action are 

 different and that the chemical histamine-liberators do not bring about dis- 

 ruption of mast cells through the agency of a blood anaphylatoxin. 



Antihistamines 



According to Dale (1950) antihistamines may act either by blocking tissue 

 receptors to circulating histamine or by interfering with the release of histamine 

 from its depots in the tissues. It was therefore of interest to see if antihistamines 

 would alter the mast-cell response to the histamine-liberators and to the 

 anaphylatoxic serum. 



It was first found that the maximal tolerated dose of 'Anthisan' (mepyra- 

 mine maleate, May and Baker) for a 200 g. rat was 0-2 ml. of a 2-5 per cent 

 solution given slowly intravenously. Fifteen minutes after giving this dose to 

 four rats, two of them each received a slow lethal injection of stilbamidine and 

 two were given a slow injection of curare as previously described. Stilbamidine 

 and curare are both toxic substances irrespective of their action as histamine- 

 liberators, and premedication with 'Anthisan' in no way reduced the lethal 

 effect of either compound; but it did appear to protect the mast cells almost 

 completely against the disruption which normally followed their injection. 

 However, premedication with 'Anthisan' did not prevent the uptake of stil- 

 bamidine by the mast cells, which showed the usual vivid fluorescence in 

 ultra-violet light. Only the subsequent disruption of the cells was suppressed 

 (Fig. 23). 



66 



