Inhibition of human pancreatic proteinases by human plasma alpha2-antiplasmin and antithrombin.
Human plasma alpha1-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 alpha1-antitrypsin are protected against the deleterious action of these enzymes by other inhibitors, we have tested their inhibition by alpha2-antiplasmin and antithrombin. We have determined the inhibition rate constants kass and calculated d(t), the in vivo inhibition time. Surprisingly, trypsin is inhibited faster by alpha2-antiplasmin [kass=2.5 x 10(6) M(-1)S(-1), d(t)=2.3 s] and antithrombin [kass=1.7 x 10(5) M(-1)s(-1), d(t)=5.8 s] than by alpha1-antitrypsin [d(t)=17 s or 116 s in alpha1-antitrypsin-sufficient or alpha1-antitrypsin-deficient 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 alpha2-antiplasmin are not physiological inhibitors of chymotrypsin and elastase. These enzymes are, however, physiologically inhibited by alpha1-antitrypsin and alpha1-antichymotrypsin even in alpha1-antitrypsin-deficient individuals. We conclude that (i) low molecular weight heparin may be helpful in the management of acute pancreatitis, and (ii) genetically determined alpha1-antitrypsin deficiency probably does not lead to a significantly increased risk of plasma protein degradation during this disease.
Nobar
Shila M
SM
Laboratoire d'Enzymologie, INSERM U392, Université Louis Pasteur de Strasbourg, F-67400 Illkirch, France.
Guy-Crotte
Odette
O
Rabaud
Michel
M
Bieth
Joseph G
JG
D000991:Antithrombins / Q000494:pharmacology*; D002918:Chymotrypsin / Q000037:antagonists & inhibitors; D006801:Humans; D007700:Kinetics; D010179:Pancreas / Q000201:enzymology*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D000979:alpha-2-Antiplasmin / Q000494:pharmacology*
D000991:Antithrombins; D015842:Serine Proteinase Inhibitors; D000979:alpha-2-Antiplasmin; D002918:Chymotrypsin