Inflammation and Related Phenomena 119 



protease group. This activation may possibly be prevented by sub- 

 stances which antagonise these enzymes in vitro, e.g. salicylate, 

 quinine or DFP. The effect of globulins and peptides on blood 

 vessels does not become apparent until one-half to two hours after 

 injury. 



Little is known of the intimate mechanism whereby histamine, 

 globulins and peptides increase capillary permeability. However, 

 there is some evidence for a final common pathway since histamine 

 renders capillaries partially refractory to the action of peptides 

 and since all direct-acting capillary permeability factors have cer- 

 tain common properties, e.g. free amino groups, action on smooth 

 muscle. The nature of this final common pathway may possibly be 

 indicated by the fact that inhibitors of the esterase-protease group 

 of enzymes, notably salicylate and quinine, suppress the increased 

 capillary permeability induced by local injection of histamine, 

 5-H.T., globulins, peptides, and histamine releasers. Thus there is 

 some evidence that all endogenous mediators of increased capillary 

 permeability may exert their effect by activating an enzyme of the 

 esterase-protease group in or near the vessel wall (Spector and 

 Willoughby, 1960a) . The substrate of this enzyme could be a pro- 

 tein or phospholipid in the capillary wall or the precursor of yet 

 another mediator substance which then acts on the blood vessel. 

 It is known that peptides are capable of activating an esterase in 

 guinea pig serum (Becker et al., 1959) and an esterase capable of 

 splitting synthetic substrates, e.g., a naphthyl acetate has in fact 

 been demonstrated in or around the walls of small blood Vessels 

 by histochemical means. Inhibitors of monoamine oxidase do 

 not lessen the effect on capillaries of histamine, globulins 

 and peptides so that it is clear that these permeability-increasing 

 compounds do not act by facilitating the enzymic destruction of 

 the adrenaline-like substance. On the other hand, in inflammation 

 induced by thermal injury the inhibitory actions of monoamine 

 oxidase inhibitors and of anti-esterases such as quinine are not 

 additive. This may mean that destruction of adrenaline-like sub- 

 stance may affect capillaries by way of the same common pathway 

 as is followed by histamine, globulins and peptides. It is of interest 

 that high concentrations of some anti-histamine drugs e.g. phener- 



