Chapter V 

 THE MAST CELL AND HEPARIN 



IN 1937, sixty years after Ehrlich's discovery, interest in the mast cell was 

 suddenly stirred by the claim that the mast cell is the site of formation or 

 storage of heparin, the natural anticoagulant of the circulating blood 

 (Holmgren and Wilander, 1937). To those who had worked on the mast cell 

 from a morphological standpoint (Michels, 1938) the new hypothesis was 

 entirely unexpected; nevertheless, at first sight it seemed unassailable. 



Scandinavian workers had for long been interested in a powerful anti- 

 coagulant, first isolated from dog liver and hence called 'heparin'. When it was 

 first discovered, heparin was thought to be a phosphatide (McLean, 1916), 

 but as a result of the tenacious researches of Jorpes (1946) and his colleagues, 

 it was eventually shown that heparin is a polymer of disaccharide units (glucur- 

 onic acid and glucosamine) strongly esterified with sulphate (Jorpes, 1936). 

 As Jorpes (1946) points out, it was the high sulphur content of the ash which 

 supplied the analytical clue not only to the unusual nature of heparin but also 

 to its remarkable inhibitory effect on the clotting process. However, it was 

 already clear that the name 'heparin' is not entirely appropriate. Charles 

 and Scott (1933, p. 434) observe that, even in the dog, 'the liver is not necessarily 

 the seat of production for heparin, nor does it contain the only reserve of heparin 

 in the body'. Whereas the liver of the dog is exceptionally rich in heparin, 

 the liver in certain other species contains only the merest traces. 



Two fresh findings combined to solve the mystery of the cytological location 

 of heparin. Lison (1935), in Belgium, had discovered that the metachromatic 

 staining reaction has histochemical significance, being positive with high 

 molecular poly-sulphuric acid esters of the type R-[OS0 3 H] n . Meanwhile, 

 Jorpes (1936) had observed that the strongly acidic heparin in solution is 

 precipitated by, and stains metachromatically with, the basic dye, toluidine 

 blue. The next step was to search the tissues for a metachromatic component 

 corresponding to sites rich in heparin. 



Holmgren and Wilander (1937) then quickly rediscovered the metachromatic 

 granules in the mast cells: cartilage, the only other common tissue component 

 which stains metachromatically is almost devoid of anticoagulant activity 

 (Jorpes, 1937). Holmgren and Wilander found mast cells to be so numerous 

 in the capsule of ox liver that they describe it as a 'pure culture of mast cells' 

 and this tissue gave the highest yield of heparin : little heparin was found in 

 the underlying parenchyma of ox liver which contains few mast cells. In 

 contrast, mast cells are numerous in the liver parenchyma of the dog, the 



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