THE MAST CELLS 



of the mast cell and the structure of the mast granule suggests a multiplicity 

 of mechanisms whereby histamine may be released. These range from the 

 total disruption of the mast cell to the quiet replacement of the histamine 

 molecule by another amine (as, for example, toluidine blue) without accom- 

 panying morphological change. The reader is referred to the excellent reviews 

 by Paton (1955, 1957, 1958) on the structure-action relationships of the many 

 histamine-liberators which are now known. Finally, there is evidence, admittedly 

 as yet fragmentary, that the granule or cell membrane may contain in its 

 structure a phospholipid capable of yielding a primary phosphatide selectively 

 sensitive to histamine, which, freed from its ionic linkage in the cell, procures 

 its own release by its surface activity on the film which surrounds it. This may 

 prove to be the point of attack of the chemical histamine-liberators. 



This last-mentioned hypothesis has recently received considerable experi- 

 mental support from the work of Uvnas (Hogberg and Uvnas, 1957; Uvnas, 

 1958o and b) in Stockholm who suggests that a basic histamine-liberator such 

 as compound 48/80 releases histamine from the mast cell, not by a mere 

 neutralization of acidic heparin in a histamine-heparin complex, but by 

 removing an inhibitor from a lecithinase situated at the mast-cell membrane. 

 The activated enzyme then brings about a lysis of the cell envelope, so permit- 

 ing the intracellular histamine to escape (Hogberg and Uvnas, 1958). 



I had myself considered the possible role of a lecithinase in the process of 

 histamine-release from mast cells (Riley, 1958a) but had failed to envisage the 

 necessary mechanism whereby a chemical histamine-liberator might influence an 

 enzymic process. However, if we not only accept Uvnas' hypothesis but make 

 the additional assumption that the enzyme is a Type-C lecithinase (Deuel, 1951 ), 

 attacking the ester link between the phosphoric acid and the alcohol, we infer 

 that its action on the various phospholipids demonstrated by Dr. Dawson in 

 mast cells would be as follows: 



Phosphatidyl choline yields a primary phosphatide and choline 



Phosphatidyl serine yields a primary phosphatide and serine 



Phosphatidyl ethanolamine yields a primary phosphatide and ethanolamine. 



From each, therefore, there is formed first, a primary phosphatide selectively 

 permeable to histamine (Hirt and Berchtold, 1952) and second, an alcohol 

 (choline, serine, ethanolamine) differing quantitatively and qualitatively from 

 one type of mast cell to another. When the effects of the three alcohols are 

 tested on mast cells in fresh tissue spreads of rat mesentery, it is immediately 

 apparent that ethanolamine is the most effective disrupter of mast cells and, 

 in fact, produces a frothy, 'honeycomb' appearance of the cytoplasm very 

 similar to that which is observed in vivo (Riley, 1953/?; Hill, 1957). 



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