Role of Enzymes in Inflammation

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In the early stage of inflammation, various zymogens, such as Hageman factor, plasminogen, kallikreinogen and the first component of complement, Cl, are activated, and these activated enzymes produce various chemical mediators, such as histamine, serotonine, anaphylatoxin and kinin, etc. The present report deals with activation of human plasma kallikreinogen and plasminogen, concomitant kinin formation, and inhibition of plasmin, plasma kallikrein and activated Cl. by various w-amino and w-guanidino acid esters. On the activation of plasminogen, kallikreinogen and kinin formation, highly complicated mechanisms have been proposed by several authors. As described in our previous reports 7, 8), both kallikrein and plasmin release kinin directly from kininogen, and no conversion of kallikreinogen into kallikrein by purified plasmin was observed under our experimental conditions. Hageman factor, which had been purified from bovine plasma, could convert kallikreinogen into kallikrein: addition of purified Hageman factor to partially purified kallikreinogen, which had been obtained from EDTA-treatment of human euglobulin fraction, increased TAMehydrolytic activity. However, no activation of plasminogen by Hageman factor was observed.<BR>In plasma there exist two types of kininogen I and, which are separated from each other with DEAE-Sephadex A-50 column chromatography 3). Actions of various kinin forming enzymes on these two types of kininogen were examined, and the kinin formed was determined by means of rat uterus. Both purified human plasmin and kallikrein activated by acetone released kinin mainly from kininogen II. On the other hand, the kinin formation by kallikrein activated by Hageman factor was observed mainly from kininogen I and poorly from kininogen II. These results show the different kinin forming activities of these enzymes, and particulary, between kallikrein activated by acetone and that by Hageman factor.<BR>Saturated aliphatic esters of amino and guanidino acid extensively inhibit trypsin, plasmin and kallikrein 11). In this report, it was found that aromatic esters, such as phenyl guanidinocaproate, phenyl and carboxyethylphenyl <I>trans</I>-4-aminomethylcyclohexanecarboxylate, exhibited a far more extensive inhibitory effect not only on the esterolytic and kinin forming activities of plasmin and kallikrein, but also ATE-hydrolytic activity of the activated first component of human complement, Cl.
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Role of Enzymes in Inflammation

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