Recombinant alpha 1-antitrypsin Pittsburgh attenuates experimental gram-negative septicemia.
|
| Abstract |
Alpha 1-antitrypsin-Pittsburgh (AT-P), a naturally occurring lethal mutation (358Met----Arg), has been genetically engineered (rAT-P). The protein has been shown to be a potent active site-directed inhibitor of thrombin and the contact enzymes Factor XIIf, Factor XIa, and kallikrein. Because activation of the contact system is known to occur in gram-negative septicemia, the authors have hypothesized that the administration of rAT-P might modulate the course of this syndrome. Yorkshire piglets anesthetized with pentobarbital and infused with viable Pseudomonas aeruginosa (2 X 10(8) CFU) were untreated (Group I) or treated with rAT-P (Group II) and studied in a 6-hour protocol. Coagulation studies revealed that rAT-P significantly inhibited the rapid decrease in the functional concentrations of Antithrombin III, Factor XI, and fibrinogen. In addition, rAT-P markedly reduced the serum levels of fibrinogen degradation products. Survival in Group II was significantly increased during 2-5 hours but not at 6 hours when the functional levels of rAT-P in plasma were the lowest. These results indicate that this recombinant inhibitor, even at low concentrations, affords protection in experimental gram-negative septicemia.
|
|---|---|
| Authors | R W Colman, D N Flores, R A De La Cadena, C F Scott, L Cousens, P J Barr, I B Hoffman, F Kueppers, D Fisher, S Idell |
| Journal | The American journal of pathology (Am J Pathol) Vol. 130 Issue 2 Pg. 418-26 (Feb 1988) ISSN: 0002-9440 [Print] United States |
| PMID | 3257651 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.) |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!