THE MAST CELLS 



3. Next, the effect on the mast cells of a group of substances, whose common 

 property is an ability to release histamine, is examined. All cause swelling, 

 degranulation and even disruption of the mast cells. The action of some of 

 these substances (e.g. stilbamidine) can be followed under the microscope by 

 taking advantage of their fluorescence in ultra-violet light. 



4. The hypothesis that the mast cells themselves contain the histamine 

 which is released is put to direct test by measuring histamine values in a series 

 of normal tissues of widely differing mast-cell content. A strongly positive 

 correlation is observed throughout. Ox liver capsule and ox visceral pleura 

 are especially rich in mast cells and histamine. A method for determining the 

 histamine content of the individual mast cell in ox liver capsule is described. 



5. Exceptionally high values for histamine are found in certain pathological 

 tissues rich in mast cells. Urticaria pigmentosa in man and mast-cell tumours 

 from domestic animals all yield exceedingly high values, sometimes measurable 

 in milligrams of histamine per gram of tissue examined. It is now the heparin 

 (measured as anticoagulant) which occasionally fails to show a correspondingly 

 high value, as, for example, in mast-cell tumours from cats. 



6. At this point in the present investigation a more specific histamine- 

 liberator became available, Compound 48 80. Its effects were therefore 

 studied on the mast-cell and histamine contents of a variety of tissues in the rat. 

 Once the histamine has been completely released, Compound 48/80 is no longer 

 toxic to the rat : long-term study of its effects is thus possible. 



7. However, when Compound 48/80 is given to mice, not more than about 

 half the available histamine can be liberated; higher doses are toxic and kill 

 the mice from causes unconnected with the release of histamine. Evidently 

 there are differences in the structure and composition of the mast cells, even 

 among closely allied species. 



8. This raises the question of the means whereby histamine is bound in the 

 mast cell. Attention is drawn to the similarity of the reactions of the mast cell 

 and of the myelin of nerve sheaths : both swell in water and in hypotonic solutions, 

 especially in the presence of alkali. The chemical histamine-liberators are also 

 bases and cause swelling of the mast cells. An enquiry into the efficiency with 

 which trichloracetic acid extracts histamine from tissue samples adds further 

 to the belief that histamine exists in the mast cells, preformed and ready for 

 release, held only by loose ionic forces within a phospholipid membrane. 

 Normally the histamine in the granule is part of a loose complex containing 

 also heparin and proteins rich in basic amino-acids. When tissues of high mast- 

 cell content, or the isolated mast granules from rats, are analysed by paper 

 chromatography it is found that they contain phosphatidyl choline (lecithin) 

 and comparatively large amounts of phosphatidyl serine. The granules from 

 rats also contain phosphatidyl ethanolamine. These phosphatides may 



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