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S.M. Nobar, O. Guy-Crotte, M. Rabaud, J.G. Bieth
Inhibition of human pancreatic proteinases by human plasma ?2-antiplasmin and antithrombin
Human plasma ?1-antitrypsin inhibits human pancreatic trypsin, chymotrypsin and elastase, which are massively released into the blood stream during acute pancreatitis. To examine whether the plasma proteins of individuals with genetic deficiency of ?1-antitrypsin are protected against the deleterious action of these enzymes by other inhibitors, we have tested their inhibition by ?2-antiplasmin and antithrombin. We have determined the inhibition rate constants k and calculated d(t), the in vivo inhibition time. Surprisingly, trypsin is inhibited faster by ?2-antiplasmin [k=2.510[6] M[-1]s[-1], d(t)=2.3 s] and antithrombin [k=1.710[5] M[-1]s[-1], d(t)=5.8 s] than by ?1-antitrypsin [d(t)=17 s or 116 s in ?1-antitrypsinsufficient or ?1-antitrypsindeficient individuals, respectively]. Low molecular weight heparin accelerates the inhibition of trypsin by antithrombin by a factor of 16 [d(t)=0.36 s]. Antithrombin and ?2-antiplasmin are not physiological inhibitors of chymotrypsin and elastase. These enzymes are, however, physiologically inhibited by ?1-antitrypsin and ?1-antichymotrypsin even in ?1-antitrypsindeficient individuals. We conclude that (i) low molecular weight heparin may be helpful in the management of acute pancreatitis, and (ii) genetically determined ?1-antitrypsin deficiency probably does not lead to a significantly increased risk of plasma protein degradation during this disease.
Biological Chemistry, Walter de Gruyter
Print ISSN: 1431-6730
Volume: 385, 05/2004
Pages: 423 - 427