Studies of inhibitors of bacterial and other hyaluronidases. I. Specific and nonspecific serum inhibitors.

There are two types of hyaluronidase inhibitor in noimal human serum; one is destroyed when the serum is heated at 55 C to 60 C for 15 to 30 min, the other is not (Thompson and Moses, 1949). The heat-labile inhibitor, referred to as the nonspecific inhibitor (NSI), is present in the serum of many different species and inhibits testicular and several bacterial hyaluronidases (Haas, 1946). The relative effectiveness of this inhibitor against different bacterial enzymes has never been critically examined (Mathews and Dorfman, 1955). Its reaction with hyaluronidase is characterized by the followving featuies: (1) it proceeds at a measurable rate (Haas, 1946; Hadidian and Pinie, 1948b); (2) is completely inhibited by concentrations of phosphate 0.05 M or higher (Haas, 1946; Hadidian and Pirie, 1948b); (3) requires the presence of magnesium or cobalt ion (Freeman et al., 1949; Hadidian, 1951) and (4) is prevented or reversed by small amounts of proteolytic enzymes (Hadidian, 1953; Hadidian and AMurphy, 1955). The heat-stable inhibitors, referred to as the specific inhibitors (SI), aire electrophoretically separable from NSI (Moore and Harris, 1949) and presumably are antibodies acting on specific enzymes (Harris and Harris, 1950; Emmart and Cole, 1955). Such inhibitors are produced in animals immunized with hyaluronidase preparations and show a high degree of specificity (Harris and Harmis, 1950; Wenner et al., 1951). Studies of the type which have revealed the characteristic features of the reaction between NSI and the testicular enzyme have not been done either with the specific inhibitors of immunized animals or ther-