114 The Chemistry of the Injured Cell 



over, there is no reason to suppose that rapid destruction in plasma 

 would prevent their effect on capillaries in inflammation. De- 

 struction by peptidases may in fact be a homeostatic mechanism 

 for inactivating these potent substances once they escape from the 

 site of the inflammatory reaction. Since there are no specific in- 

 hibitors of the formation and activity of kinins it is as yet im- 

 possible to test their role in inflammation by the administration of 

 such compounds. 



PROTEINS 



There exists in the globulin fraction of the plasma proteins of 

 all mammalian species yet tested, a substance capable of increasing 

 capillary permeability in very low concentration (Miles and Wil- 

 helm, 1955; Wilhelm et al., 1958) . This globulin is present nor- 

 mally as an inert precursor that can be activated by a variety of 

 procedures including dilution with saline, contact with organic 

 solvents, and incubation with minced tissues. It is therefore an ob- 

 vious candidate for the role of mediator of the vascular changes of 

 acute inflammation. The protein could act directly on vessels 

 (possibly enzymically) or could be either protease or, less likely, 

 substrate in the formation of peptides of the kinin type. 



A substance with properties similar to those of the plasma 

 globulin can be obtained by extracting a variety of minced tissues, 

 e.g., lung, skin or spleen with isotonic saline. The extracts con- 

 tain in active form a powerful capillary permeability factor. It is 

 not yet certain whether the active principle of these tissue ex- 

 tracts is identical with the substance obtained from plasma but 

 they have up till now been assumed to be of similar nature. It is 

 also known that certain mucoproteins, derived for example from 

 glandular secretions of the guinea pig are highly active in increas- 

 ing capillary permeability. In the case of all these proteins it is not 

 yet known whether their action is direct or whether they exert 

 their effect by giving rise to kinins. However, it is established that 

 certain enzymes of the protease and esterase group, will cause in- 

 creased capillary permeability on injection into the tissues of liv- 

 ing animals quite possibly by a direct action on the vascular wall. 

 Trypsin is one such enzyme, but as this substance is a histamine 



