Chapter XVII 



GENERAL DISCUSSION: FUNCTIONS OF THE 

 TISSUE MAST CELLS 



EIGHTY years have now passed since Ehrlich first clearly described and 

 named the tissue mast cells, and we are still far from understanding 

 their biological significance in the organism. Ehrlich himself believed 

 that the mast cells are concerned in some way with the nutrition of the connective 

 tissues. None of the twenty-five hypotheses listed sixty years later by Michels 

 (1938) entirely supplanted this first attempt to endow the mast cell with a 

 specific function. 



However, in that same year (1937) Scandinavian workers succeeded in 

 tracing heparin to the mast cells, a discovery which was widely accepted as the 

 final answer to Ehrlich's 'riddle'. 



Briefly, the Scandinavians based their new hypothesis on two main premises, 

 both of which deserve the most careful scrutiny. These are first, the assumption 

 that the heparin which they succeeded in extracting chemically from dog liver 

 (hence Howell's choice of the name, 'heparin') or from other tissues rich in 

 mast cells is the natural anticoagulant of the circulating blood; second, that 

 the perivascular distribution, so characteristic of the mast cells, likewise indi- 

 cates a haemic function, in this case, the prevention of intravascular thrombosis 

 by the secretion of anticoagulant through the vessel wall. 



Certainly, the first premise seemed to derive formidable support from the 

 finding that heparin does escape from the dog's liver into its blood in peptone 

 and in anaphylactic shock. This led to the further assumptions, (a) that the 

 conditions of peptone shock merely exaggerate a normal state of affairs (i.e. 

 that a pathological process is an extension of a physiological process) and {b) 

 that the dog is characteristic of other animal species with respect to the function 

 of its mast cells. It was unfortunate that the original investigation did not 

 compare conditions in the dog with those in the cat, guinea pig or rat. Instead 

 there came to be constructed an inverted pyramid of reasoning, founded on 

 the findings in a single species and upon a pathological condition which has 

 no known counterpart elsewhere. It will be recalled that we found very low 

 heparin values in cat mastocytomas in which the granules are brilliantly 

 metachromatic and in which the histamine values are often very high indeed; 

 and we could obtain no evidence of a release of heparin into the blood of rats. 

 Other workers have likewise failed to detect changes in blood coagulation 

 either in experimental animals or in patients with widespread urticaria pig- 

 mentosa. Whereas heparin is present in many tissues and organs, there is 



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