THE MAST CELLS 



it is noteworthy that Sir Henry Dale himself warns us against the easy assump- 

 tion that anaphylaxis and the release of histamine are synonymous. In his 

 own words (Dale, 1954, p. 210), 'Anaphylaxis ... is a phase of immunity, in 

 which a precipitating antibody is located in such a relation to living cells of the 

 fixed tissues or, in certain cases, of the circulating blood, that its union with the 

 reinjected antigen subjects the cells to a sudden injury. To this injury, as to 

 injury of any kind, these cells respond by the liberation of substances normally 

 held in their protoplasm.' Thus the argument might be extended, that if the 

 injured cell contains heparin it will release heparin, that if it contains histamine 

 it will release histamine, and that if both are present in the same cell, both will 

 be released during anaphylactic shock. We know that the release of histamine 

 in anaphylaxis is a comparatively common event. As mentioned above, only 

 the dog releases at the same time sufficient heparin to cause an obvious pro- 

 longation in the clotting time of its blood. 



The question thus arises why does the dog alone show an incoagulability 

 of the blood in shock states? A partial answer, at least, can be given on the 

 factual observations that not only is the heparin from dog tissues a more 

 efficient anticoagulant than are the heparins of other species (Jorpes, 1946; 

 Bell and Jaques, 1956), but that even when the suprahepatic veins in the dog 

 are closed by spasm of their muscular walls (as they are when there is histamine 

 in circulation) there is still available the thoracic duct to lead the histamine 

 and heparin from the 'shock organ', the liver, direct to the blood stream (Riley, 

 1955; White and Woodard, 1957): an enhancement of the lymph flow through 

 the thoracic duct during shock states in the dog has long been known to occur 

 (Petersen and Levinson, 1923; Drinker and Yoffey, 1941). In this way the 

 heparin released in the liver of the dog during anaphylaxis avoids contact with 

 the connective tissues and filtration through the lymph nodes. In other species 

 the mast cells are not in a position to discharge their products directly into the 

 blood. Therefore, it can be said that there is no strong reason to reject the 

 idea that both histamine and heparin may come from a common source, the 

 mast cell, in all species. 



Turning next to conditions in man we find even more positive evidence of 

 a relationship between the mast cell and histamine. Some years before Ehrlich 

 first described the mast cells, Nettleship (1869) had observed that slight trauma 

 to a focus of the skin disease, urticaria pigmentosa, leads to local swelling and 

 a reddening of the surrounding skin. This is the reaction which Sir Thomas 

 Lewis (1927) described as the 'triple response', a reaction later shown by Sir 

 Henry Dale (1929) to be the visible evidence of the release of histamine in the 

 skin. Very recently a case of widespread urticaria pigmentosa has been 

 described in which the child suffered from recurrent histamine shocks; but there 

 were no changes in the coagulability of the blood (Bloom et al, 1958a). Histo- 



36 



