DISCUSSION 



little evidence that heparin is a normal constituent of blood. Even a study of 

 the histological relationship of mast cells to blood vessels in the rat led me to 

 conclude that the mast cells fulfil their cycle in the connective tissues and do not 

 secrete their contents directly into the blood stream. 



It was thus the more fortunate that I first encountered the tissue mast cell, 

 not in relation to the effects of heparin on the blood, but in a connective tissue 

 reaction in the skin of mice treated with a carcinogen. This led to a search 

 for a tissue function of the mast cell and to the study of the few conditions 

 then known in which the mast cell appears to be involved. Such conditions 

 seemed to have little enough in common, except, perhaps, the participation of 

 histamine : it was this that led to the present enquiry and to the discovery that 

 the tissue histamine resides in the same cell as the tissue 'heparin', a finding 

 which has since been abundantly confirmed elsewhere (Mota et al, 1954; Benditt 

 et al, 1955; Graham et al, 1955; Wegelius et al, 1955; Arvy et al, 1956; Asboe- 

 Hansen and Wegelius, 1956; Keller and Burkard, 1956; Werle and Amman, 

 1956; Hill, 1958). Other workers have shown that much of the histamine in 

 blood, at least in man, is likewise contained in the blood mast cells, or basophils 

 (Graham et al, 1955; Code and Mitchell, 1954, 1957). The eosinophil, once 

 thought to be the main carrier of histamine, appears to be more concerned with 

 the detoxification and disposal of tissue histamine than with its elaboration 

 (Ehrich, 1953; Samter, 1953; Vaughn, 1953; Vercauteren, 1953; Archer, 1956). 

 We have often seen eosinophils in our material, but generally in situations in 

 which histamine is being released from mast cells. 



It may be useful in summing up the present work to comment briefly on 

 the ground that has been covered, using the same numerical division of the 

 matter as in the text: — 



In Part I, a preliminary survey of the tissue mast cells in organisms of 

 increasing complexity confirms Ehrlich's view that the cells with basophilic, 

 metachromatic granules (his 'Mastzellen') are healthy, functioning cells of 

 the connective tissues. In certain primitive species mast cells are present before 

 the necessity for a blood vascular system has arisen. Fibroplasia, normal or 

 pathological, is consistently followed by the development of tissue mast cells. 



In Part II, a brief introduction (1) sets out the reasons for my own growing 

 belief that the mast cell is more concerned with events in the tissues than in the 

 blood, and that the mast cells may play a part in the release of histamine. 



2. Detailed examination of the distribution of mast cells in the ox and rat, 

 using the method of tissue spreads, emphasizes the enormous numbers of mast 

 cells in the serous membranes, as well as around small blood vessels; even the 

 perivascular mast cells seem to move away from the vessels as the cells mature. 

 Mast cells are always to be found in young vascular connective tissue under- 

 going fibrillogenesis. 



L 161 



