356 IMMUNO-CATALYSIS 



the toxin as responsible for the injury to tissues and thereby the 

 hberation of histamine.* Experiments upon the perfused lungs of 

 cats showed the liberation of histamine from these organs by toxin, 

 though it was much less active than snake venom. Impurities were 

 found not to be responsible for this eflPect because ovemeutralized 

 purified toxin failed to cause any detectable output of histamine in 

 the perfusate. A parallelism between the degree of tissue injury and 

 the amount of histamine liberated was established. They stated that 

 it is probable that the action of toxin at the site of histamine libera- 

 tion in the lungs contributes to the edema which is so frequently 

 observed in all of the three species studied. It may also contribute to 

 the liberation of adrenalin from the suprarenals of the rabbit. 



As with snake venom, Kellaway and Trethewie observed that the 

 toxin liberated adenyl compounds. The cardio-depressant substances 

 set free by the toxin behaved like adenosine and adenylic acid, being 

 destroyed by the enzyme present in the tissues and in perfusates. 

 These facts showed that toxin directly or indirectly sets in motion in 

 the organism an enzyme or enzymes attacking nucleoproteins of tis- 

 sues. To trace the cardio-depressant effect to the nucleic acid deriva- 

 tives, the effects of choline derivatives in extracts and perfusates were 

 eliminated by repeated atropinization of the test preparation. The 

 effects of toxin in the perfusate and extracts were eliminated by over- 

 neutralization of each sample vdth a powerful antitoxin, and the effects 

 of impurities in the over-neutralized mixtures were avoided by the 

 use of doses which contained too large an amount of toxin. 



*In connection with the nature and types of factors injurious to cells, the observa- 

 tions of Menkin (1943) are of interest. He has described an injury factor, tentatively 

 called "necrosin," which is not histamine. It is present in the inflammatory exudates 

 of dogs and man, and is associated or identical with the euglobulin fraction. It is 

 thermolabile and non-diffusible. The dialyzed euglobulin fraction of exudates causes 

 severe edematous inflammation in rabbits characterized by lymphatic blockade. In- 

 jected subcutaneously, it produces intense local redness, edema and frequent central 

 necrosis, and erythema and congestion in the tributary lymphatic nodes. Intravenous 

 administration of necrosin in a dog is followed by a marked leukopenia accompanied 

 by transient toxic manifestations such as vomiting and diarrhea. It markedly hastens 

 the rate of coagulation of blood in vitro. The question as to whether this is due to 

 thrombokinase associated vdth necrosin in the Tatter's present state of purification is 

 unanswered at present. 



Sera containing large quantities of hemolyzed material, or highly lipemic sera, are 

 apt to contain necrosin. It can be extracted from the blood serum of an animal which 

 has a concomitant acute inflammation. It is absent in the euglobulin fraction of the 

 blood serum of normal dogs and man. These facts suggested to Menkin that necrosin 

 is liberated from injured cells. 



