INTRODUCTION 



logically, the beautiful description of Unna (1896) has been many times 

 confirmed that the lesion of urticaria pigmentosa is an aggregation of mast 

 cells. 



The discovery of the specific histamine-liberators 



It will be seen from the foregoing appraisal that there were two main 

 problems in mind when the present work was begun: first, is the primary 

 function of the mast cell to elaborate an anticoagulant for the circulating 

 blood? Second, is the mast cell also a potent source of tissue histamine? 



An approach to the first problem was made by examining the normal 

 distribution of mast cells in as many tissues and species as possible, seeking 

 evidence for or against the theory that the metachromatic substance in the mast 

 granules (heparin?) is discharged direct into the blood. This work will be 

 described first in the account which follows. Then in 1949 a paper appeared 

 in the Journal of Physiology which seemed to offer a new and more direct 

 approach to the second question, the relationship of the mast cell to tissue 

 histamine. This was the account by Macintosh and Paton, working at the 

 National Institute of Medical Research, of a series of organic bases whose 

 pharmacological action appeared to be a specific release of histamine. These 

 compounds induced a 'triple response' when injected locally into the skin 

 of man; they produced a profound, though significantly delayed, fall of blood 

 pressure when injected intravenously into a cat; and in the dog their effects 

 resembled to a remarkable degree the syndrome of anaphylactic or peptone 

 shock — a fall in blood pressure and a prolongation of the clotting time of the 

 blood. The discovery of the histamine-liberators offered a means of expanding 

 the present investigation. The general plan of the work is given below. 



1. To continue to obtain further information on the normal morphology 

 and distribution of the mast cells in various species with a view to deciding 

 whether they are functionally related to the blood or to the tissues: in particular 

 to examine the relationship of mast cells to blood vessels. 



2. To study the mast cells in pathological states, especially where there is 

 clinical evidence of a release of histamine. (As stated above, the release of 

 histamine is of more general occurrence than the release of anticoagulant 

 heparin.) 



3. To search for at least one species of laboratory animal suitable for 

 experimental studies involving an artificial alteration in the content of its tissue 

 mast cells, or tissue histamine, and to compare such changes: in particular, 

 to observe the effect on the mast cells of the newly discovered histamine- 

 liberators. 



4. To determine, by direct assay, whether there exists a positive correlation 

 between the mast-cell content of a tissue and its histamine value. 



37 



