PMID- 3500941 OWN - NLM STAT- MEDLINE DCOM- 19880127 LR - 20171213 IS - 8750-7587 (Print) IS - 0161-7567 (Linking) VI - 63 IP - 5 DP - 1987 Nov TI - Augmentation of lung antineutrophil elastase capacity with recombinant human alpha-1-antitrypsin. PG - 2015-23 AB - To evaluate the potential use of recombinant DNA-produced alpha-1-antitrypsin (alpha-1-AT) to augment the lung antineutrophil elastase defenses in alpha-1-AT deficiency, we compared the kinetics of intravenously administered recombinant produced alpha-1-AT (r alpha-1-AT) and purified normal human plasma alpha-1-AT (p alpha-1-AT) in the blood and lung of rhesus monkeys. The r alpha-1-AT was produced in yeast transformed with an expressing plasmid containing a full-length human alpha-1-AT complementary deoxyribonucleic acid and purified to greater than 99% homogeneity. The r alpha-1-AT has a molecular weight of 45,000, no carbohydrates, and is identical in sequence to normal plasma alpha-1-AT except for an additional N-terminal acetylmethionine. Despite its lack of carbohydrates, the r alpha-1-AT inhibited human neutrophil elastase with an association rate constant similar to that of p alpha-1-AT. Rhesus monkeys were infused intravenously with 120 mg/kg of r alpha-1-AT (n = 13) or p alpha-1-AT (n = 12) and the serum, urine, and lung epithelial lining fluid (ELF) concentrations of these molecules quantified at various intervals.(ABSTRACT TRUNCATED AT 250 WORDS) FAU - Casolaro, M A AU - Casolaro MA AD - Pulmonary Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892. FAU - Fells, G AU - Fells G FAU - Wewers, M AU - Wewers M FAU - Pierce, J E AU - Pierce JE FAU - Ogushi, F AU - Ogushi F FAU - Hubbard, R AU - Hubbard R FAU - Sellers, S AU - Sellers S FAU - Forstrom, J AU - Forstrom J FAU - Lyons, D AU - Lyons D FAU - Kawasaki, G AU - Kawasaki G AU - et al. LA - eng PT - Comparative Study PT - Journal Article PL - United States TA - J Appl Physiol (1985) JT - Journal of applied physiology (Bethesda, Md. : 1985) JID - 8502536 RN - 0 (Blood Proteins) RN - 0 (Protease Inhibitors) RN - 0 (alpha 1-Antitrypsin) SB - IM MH - Animals MH - Blood Proteins/*metabolism MH - Bronchoalveolar Lavage Fluid/*metabolism MH - Electrophoresis, Polyacrylamide Gel MH - Epithelium/metabolism MH - Half-Life MH - Humans MH - Lung/metabolism MH - Macaca mulatta MH - Molecular Weight MH - Protease Inhibitors/*metabolism MH - alpha 1-Antitrypsin/*pharmacokinetics EDAT- 1987/11/01 00:00 MHDA- 1987/11/01 00:01 CRDT- 1987/11/01 00:00 PHST- 1987/11/01 00:00 [pubmed] PHST- 1987/11/01 00:01 [medline] PHST- 1987/11/01 00:00 [entrez] AID - 10.1152/jappl.1987.63.5.2015 [doi] PST - ppublish SO - J Appl Physiol (1985). 1987 Nov;63(5):2015-23. doi: 10.1152/jappl.1987.63.5.2015.