DISCUSSION 



constitute a 'trigger' which enables histamine to escape from the intact granule 

 or cell. According to Uvnas, a chemical histamine-liberator removes an 

 inhibitor from a lecithinase at the mast-cell membrane. It is suggested that if 

 this should prove to be a Type-C lecithinase there would be formed a primary 

 phosphatide permeable to histamine and alcohols varying quantitatively and 

 qualitatively from one species of mast cell to another. At the same time it is 

 emphasized that the classical histamine-liberators produce pathological effects 

 and that under normal circumstances it may be possible to release histamine 

 without accompanying morphological changes in the mast cell. 



9. Not all histamine is held in mast cells and responds to the action of the 

 chemical histamine-liberators. The pyloric mucosa has a high histamine 

 content, though it is poor in mast cells. The histamine value of rat pyloric 

 mucosa actually rises as histamine is released from mast cells elsewhere. 



10. The function of heparin, the second major component of the mast 

 granule, is next examined and an hypothesis is suggested to account for the 

 rapid release of heparin into the blood of the dog during peptone shock. The 

 shock organ of the dog is the liver, and the heparin which can be extracted from 

 it is an exceptionally efficient anticoagulant. The dog is unique in that it has 

 a direct pathway leading from shock organ to blood, the thoracic duct, which 

 by-passes the connective tissues. Thoracic duct lymph quickly becomes 

 incoagulable during peptone shock. 



1 1 . When comparable conditions in the rat are examined, no evidence can 

 be found that active anticoagulant reaches the rat's blood as the mast cells are 

 destroyed. In fact, much of the heparin remains trapped locally in the connec- 

 tive tissues. It is suggested that the natural function of the mast cell is to store 

 and release mucopolysaccharides for the connective tissues. The carbohydrate 

 precursor substance is formed mainly by fibroblasts (since fibroblastic activity 

 normally precedes the appearance of mast cells) and becomes a temporary 

 component of the intercellular ground substance. With the onset of fibrillo- 

 genesis, excess ground substance is broken down, rebuilt and stored in altered, 

 sulphated form (heparin) in the granules of the tissue mast cells, whence it can 

 later be released and be again ingested by cells of the connective tissues. This 

 cyclic process begins and is widespread in the embryo, and recurs locally in the 

 tissues in adult life in response to 'trauma' or an acute watery oedema. A 

 massive release of the stored mucopolysaccharide, still sulphated, may result 

 in its overflow into the blood and the consequent manifestation of its anti- 

 coagulant properties. 



12. Much of the experimental work on histamine in the past concerned its 

 effects on the skin. Mast cell-histamine 'profiles' of skin from man, cattle, 

 cat, mouse and rat show a close relationship between their mast-cell and 

 histamine contents. 



163 



