FOREWORD 



cells were later found to be conspicuously abundant. It was apparently this 

 association of the dog's liver with the production of heparin, which first led 

 Dr. Riley, and those who became associated with him, to consider the possi- 

 bility that the mast cells might also be the source of the histamine; since the 

 anaphylactic shock and analogous reactions, in the form characteristic of the 

 dog, were known already to be due, essentially, to the effects of histamine and 

 heparin poured into the general circulation, as the result of a primary reaction 

 in the liver. Dr. Riley and his co-workers were thus led to make a more general 

 survey of the relation between the abundance, on the one hand, of mast cells 

 in different organs and tissues of a number of species, including examples of 

 mast-cell tumours, and the yields, on the other hand, of histamine obtainable 

 by extraction from the same normal and pathological sources. I do not doubt 

 that any careful student of their results will find that the evidence here presented 

 shows a highly significant correlation between the mast-cell content of solid 

 organs and their yield of histamine to artificial extraction; and such a student 

 will surely be impressed, as I am, with the reasonableness of the deduction that 

 the mast cells in such tissues, and, indeed, the characteristic, basophile, meta- 

 chromatically staining granules which occupy so much of the cytoplasm of 

 those cells, are by far the most probable source of that histamine. 



It must be borne in mind, on the other hand, that this staining of the 

 mast-cell granules does not, in itself, provide evidence for the presence in them 

 of histamine. Histamine, on the contrary, being itself a base, has a special 

 affinity for the acidic dyes, such as eosin and phloxin, with which it combines 

 in vitro to form precipitates. Before the demonstration by Dr. Riley and his 

 colleagues of the connexion between mast cells in a tissue and its yield of 

 histamine, there had been highly suggestive evidence of a similar association 

 between the yield of histamine from the blood of different animal species, 

 including that of man, and its richness in white cells with an eosinophile 

 granulation. In those of us who were familiar with these earlier observations, 

 the news of the discovery that, in the tissues, the occurrence of histamine was 

 associated with that of the basophile mast cells, produced, at first glance, a 

 sense of paradox, or conflict of evidence. And it seems tp me that we have the 

 more reason for gratitude to Dr. Riley and his co-workers for having gone 

 steadily forward, undeterred by any such prejudice, to collect and assemble the 

 data, which have now so abundantly confirmed their first observations. For 

 my own part, I am expecting that the new association which they have so 

 convincingly established, between histamine and the heparin-containing mast- 

 cells of the tissues, will be found to have an increasing importance, for the 

 assignment to histamine, and to the other amines, such as serotonin, now coming 

 into view as mast-cell constituents, of their various functional roles in a range 

 of physiological and pathological reactions. H R nAT F 



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