THE PERMEABILITY GLOBULINS OF HUMAN SERUM AND THE BIOCHEMICAL MECHANISM OF HEREDITARY ANGIONEUROTIC EDEMA

The two permeability globulins, PF/dil.l and serum kallikrein,2 are apparently found in many, and possibly all, mammalian species.t They both exist in an inactive forrn in serum but can be activated by a number of the same procedures. Injection of either the activated form of PF/dil. or serum kallikrein into the appropriate animal will yield evidence of increased vascular permeabiiity. Both the permeability globulins are enzymes, splitting TAMe (p-toluene sulfonyl Larginine methyl ester) . In addition, they are both inhibitable by soybean trypsin inhibitor and by di-isopropylphosphofluoridate ( D F P ) , but not by ovomucoid. Because of these many similarities, a number of investigators suggested that these two permeability globulins are actually the sarne substance which happened to be given different names. Recent work, however, from our laboretory, which we will briefly describe, has clearly established that PF/ dil. and serum kallikrein exist in human qerurn as two distinct f a c t o r ~ . ~ ~ In addition, we wish to review the work, indicating the possible implication of these globulins in the biochemical mechanism of the genetically determined disease, hereditary angioneurotic edema.