298 IMMUNO-CATALYSIS 



of some species and of occasional human beings in routine fibrin clot 

 tests with positive staphylococci is due to a deficiency of an activator 

 which is present in testicular extract and fresh human and rabbit 

 serum. When this activator was added to a non-clotting system it 

 readily formed clot. The effect of the addition of activator was also ob- 

 served by promoting the inhibition of phagocytosis in a system contain- 

 ing plasma of certain species which failed to clot when the activator 

 substance was not added. Smith, et al. (1947) reported that the intra- 

 dermal inoculation of a guinea pig with non-clotting staphylococcus 

 results at most in a trivial reaction in spite of its a-toxigenicity (a-he- 

 molysin). In contrast, guinea pigs treated with human plasma, contain- 

 ing the activator, showed striking results. In every case a large 

 edematous, inflammatory swelling developed, followed by extensive 

 abscess formation and necrosis. With the larger doses of the staphylo- 

 coccus, ulceration ensued with the free discharge of pus, and the 

 spread of infection along the flanks and to the mid-abdominal line 

 necessitated early sacrifice of the animal. This same dose of human 

 plasma, given without staphylococci, was without apparent effect 

 apart from the transient swelling produced by the large inoculum. 



Smith, et al. (1947) were cognizant of the fact that the extensive 

 cellular necrosis of the characteristic focal lesions is evidence of 

 toxic action in which clotting factor can have no direct part; these 

 indications were considered to be due to the production of a-toxin, 

 leucocidin and possibly other unknown tissue toxins. Toxin, however, 

 cannot be elaborated until the organism has gained a foothold in the 

 host and begun to multiply, and they suggested that at the initial stage 

 of natural infection with a small number of staphylococci, coagulase 

 production is absolutely essential if the infection is to progress. 

 Subsequently, the clotting factor may aid the further multiplication of 

 the organism in defiance of the ensuing phagocytic response, and may 

 determine the outcome when infected emboli are transported to other 

 sites. 



d. Comment on the Nature of the Staphylococcal Clotting Factor. 

 The ability of Staphylococcus aureus ^pyogenes') to clot blood or 

 plasma was observed several decades ago. Despite a considerable 

 number of studies the chemical nature and the mechanism of its action 

 have, as yet, remained obscure. Recently, Smith and Hale (1944) re- 

 ported the results of a fairly comprehensive study. The conclusions 



