The Presence of Two Permeability Globulins

Among the substances in mammalian sera that increase vascular permeability under experimental conditions are two globulins, the permeability globulins. The first, kallikrein, was originally described by Frey (2); the second, PF/dil, was first described by Mackay, Miles, Shachter, and Wilhelm (3). The permeability-increasing activity of kallikrein appears to be mediated through the enzymatic generation of the polypeptide bradykinin (4), whereas the mechanism of PF/dil's action is still uncertain. The role of the permeability globulins in the biology of living organisms is not entirely known. Bradykinin is one of the most potent vasodilator substances known (5). It not only causes vasodilation and increased vascular permeability, but produces pain and the local accumulation of leukocytes (6), and therefore has been suggested as a mediator of the inflammatory response. The permeability globulins have not as yet been implicated directly in the pathogenesis of a known human disease; however, there is evidence to indicate that a basic defect in the genetically determined disease hereditary angioneurotic edema is the lack of a permeability globulin inhibitor (7). Kallikrein may, in addition, have a hormonal role in bringing about the functional vasodilatation of actively secreting salivary glands and the heat vasodilatation of skin (8). Further, hypotensive vasodilator substances similar to, bradykinin have been evoked in tissues by axon reflex (9). It has been suggested that activation of permeability and hypotensive factors of this sort may be operative in states of shock. Both kallikrein and PF/dil can be obtained from serum after proper activation, and both cause hypotensive responses in addition to increasing vascular permeability in test animals. Both have associated esterase activity, and are inhibited by diisopropyl phosphofluoridate (DFP) and soy-