Casolaro M A, Fells G, Wewers M, Pierce J E, Ogushi F, Hubbard R, Sellers S, Forstrom J, Lyons D, Kawasaki G
Pulmonary Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892.
J Appl Physiol (1985). 1987 Nov;63(5):2015-23. doi: 10.1152/jappl.1987.63.5.2015.
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)
为评估重组DNA生产的α-1抗胰蛋白酶（α-1-AT）在α-1-AT缺乏症中增强肺部抗中性粒细胞弹性蛋白酶防御功能的潜在用途，我们比较了恒河猴静脉注射重组生产的α-1-AT（rα-1-AT）和纯化的正常人血浆α-1-AT（pα-1-AT）后，其在血液和肺中的动力学变化。rα-1-AT是在经含有全长人α-1-AT互补脱氧核糖核酸的表达质粒转化的酵母中产生的，并纯化至同质性大于99%。rα-1-AT分子量为45,000，无糖基，除了额外的N端乙酰甲硫氨酸外，其序列与正常血浆α-1-AT相同。尽管rα-1-AT缺乏糖基，但它抑制人中性粒细胞弹性蛋白酶的结合速率常数与pα-1-AT相似。给恒河猴静脉注射120mg/kg的rα-1-AT（n = 13）或pα-1-AT（n = 12），并在不同时间间隔对这些分子的血清、尿液和肺上皮衬液（ELF）浓度进行定量。（摘要截短于250字）
