McClean1 and Hoffman and Duran-Reynals2 established the existence in the mammalian testicles of factors which modify the permeability of connective tissue. Later work established the wide distribution in nature of similar factors as well as their enzymic character. The most important sources of "spreading factor" known today are mammalian testes, invasive bacteria, snake venom and leech extracts. As noted in a previous editorial in The Journal, Chain and Duthie3 regard the enzyme hyaluronidase and the spreading factor as the same substance. They showed that fairly pure preparations of testicular spreading factor also possess hyaluronidase activity. Hobby and his co-workers have shown that all preparations which contain hyaluronidase also contain the spreading factor. Hyaluronidase was shown to possess a variety of biologic activities such as bacterial invasiveness and fertilization of the mammalian ovum. Thus hyaluronidase not only produces the spreading reaction but also has the activity to decapsulate
HYALURONIDASE (THE SPREADING FACTOR) IN HYPODERMOCLYSIS. JAMA. 1947;135(5):289. doi:10.1001/jama.1947.02890050029009
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