依格林c和分泌型白细胞蛋白酶抑制剂对人、羊和狒狒中性粒细胞弹性蛋白酶的抑制作用。

Inhibition of human, ovine, and baboon neutrophil elastase with Eglin c and secretory leukocyte proteinase inhibitor.

作者信息

Junger W G, Hallström S, Redl H, Schlag G

机构信息

Department of Surgery, University of California San Diego.

出版信息

Biol Chem Hoppe Seyler. 1992 Mar;373(3):119-22. doi: 10.1515/bchm3.1992.373.1.119.

DOI:10.1515/bchm3.1992.373.1.119

PMID:1350199

Abstract

The association rate constants (kon) of human, ovine, and baboon neutrophil elastase with two recombinant serine proteinase inhibitors (Eglin c, secretory leukocyte proteinase inhibitor) were compared. The association rate constant of sheep leukocyte elastase (SLE) with Eglin c is about 100 times lower (kon = 2.2 x 10(5) M-1s-1) than that of human elastase (kon = 2.4 x 10(7) M-1s-1). Baboon elastase, however, is as effectively blocked with Eglin c (kon = 2.5 x 10(7) M-1s-1) as human elastase. Secretory leukocyte proteinase inhibitor (SLPI) blocks the elastase of all three species with high efficiency; baboon elastase shows the highest association rate constant (kon = 5.6 x 10(7) M-1s-1) followed by human elastase (kon = 4.1 x 10(7) M-1s-1) and finally sheep elastase (kon = 1.2 x 10(7) M-1s-1). These findings demonstrate marked differences in the inhibition kinetic properties of ovine and human elastase. Concerning a future clinical application of proteinase inhibitors, the baboon seems a more suitable model than sheep to evaluate the effects of Eglin c and SLPI, since both inhibitors block baboon and human elastase with comparable efficiency.

摘要

比较了人、羊和狒狒中性粒细胞弹性蛋白酶与两种重组丝氨酸蛋白酶抑制剂（埃格林c、分泌型白细胞蛋白酶抑制剂）的结合速率常数（kon）。羊白细胞弹性蛋白酶（SLE）与埃格林c的结合速率常数（kon = 2.2×10⁵ M⁻¹s⁻¹）比人弹性蛋白酶（kon = 2.4×10⁷ M⁻¹s⁻¹）低约100倍。然而，狒狒弹性蛋白酶被埃格林c阻断的效率（kon = 2.5×10⁷ M⁻¹s⁻¹）与人弹性蛋白酶相同。分泌型白细胞蛋白酶抑制剂（SLPI）能高效阻断这三种物种的弹性蛋白酶；狒狒弹性蛋白酶的结合速率常数最高（kon = 5.6×10⁷ M⁻¹s⁻¹），其次是人弹性蛋白酶（kon = 4.1×10⁷ M⁻¹s⁻¹），最后是羊弹性蛋白酶（kon = 1.2×10⁷ M⁻¹s⁻¹）。这些发现表明羊和人弹性蛋白酶在抑制动力学特性上存在显著差异。关于蛋白酶抑制剂未来的临床应用，狒狒似乎比羊更适合作为评估埃格林c和SLPI效果的模型，因为这两种抑制剂阻断狒狒和人弹性蛋白酶的效率相当。