THE MAST CELLS 



Ehrlich's original conception, that the mast cell is concerned with events in 

 the tissues rather than in the circulating blood: in particular it seemed that the 

 mast cell might be involved in the problem of tissue histamine. 



The mast cell and histamine 



As long ago as 1880, Schmidt-Miilheim had shown that the dog reacts to an 

 intravenous injection of peptone by a severe shock accompanied by a remark- 

 able incoagulability of the blood. Almost a quarter of a century later Portier 

 and Richet (1902) described a similar syndrome in dogs receiving a second dose 

 of a foreign protein to which they had become sensitized; this acquired hyper- 

 sensitivity they named 'anaphylaxis'. The so-called 'anaphylactic poison' 

 causing the shock was shown in 1932 by Gebauer-Fuellnegg and others to be 

 due to histamine, but it was not till 1938 that Wilander explained the in- 

 coagulability by demonstrating also a gross increase of the heparin in the 

 circulating blood. More recently Rocha e Silva and his colleagues (1947) 

 obtained large yields of both substances from the isolated dog's liver perfused 

 with peptone or the specific antigen, and their findings have been confirmed 

 (Jaques et al, 1954). In retrospect it is curious that no one seems to have 

 thought that the histamine might also come from the mast cells, of which there 

 are many in the liver of the dog (Nagayo, 1928, and cf. also Fig. 1). The specula- 

 tion of the time was that since heparin is an acid and histamine a base, the 

 heparin in shock states is released either to neutralize the histamine causing 

 the shock or to oppose any increased clotting tendency of the blood. Testing 

 this hypothesis, I found that an intravenous injection of histamine into the 

 normal dog had no obvious effect on its clotting time, that peptone shock could 

 be readily elicited in the fully heparinized dog, and that an intravenous injec- 

 tion of a mixture of heparin and histamine was followed by the clinical signs of 

 both — incoagulability of the blood and a fall in blood pressure. There was, 

 in fact, no apparent antagonism between the two substances in the circulating 

 blood, and no reason therefore for postulating that they must be derived from 

 different sources in the tissues. The question thus became: could they arise 

 together — even from the same cell ? 



This may now seem a somewhat obvious question to ask. However, at 

 that time there was a distinct mental barrier against regarding heparin as 

 anything but a natural anticoagulant. The existence of such a physiological 

 anticoagulant had for long been predicted; its discovery accorded well with 

 current views on blood coagulation. What perhaps is not adequately appreci- 

 ated, even today, is that the hypothesis of a slow release of heparin into the 

 blood as a natural anticoagulant rests on the findings in this single species, 

 the dog, in which the violent release of heparin in shock states was assumed to 

 be an exaggeration of a normal process. Yet the dog is the only animal known 



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