Hammond G L, Smith C L, Paterson N A, Sibbald W J
Department of Obstetrics and Gynecology, University of Western Ontario, Victoria Hospital, London, Canada.
J Clin Endocrinol Metab. 1990 Jul;71(1):34-9. doi: 10.1210/jcem-71-1-34.
In human blood, cortisol is transported by a plasma protein known as corticosteroid-binding globulin (CBG). As anticipated from primary structure comparisons of CBG and alpha 1-proteinase inhibitor (A1-PI), CBG acts as a substrate for neutrophil elastase. However, unlike A1-PI, CBG does not alter the activity of this enzyme, but is cleaved by it at a single location close to its carboxy-terminus, and this reduces its molecular size by 5 kDa with the concomitant release of more than 80% of CBG-bound cortisol. Three small molecular size fragments are detected after elastase cleavage, and carbohydrate analysis of these fragments suggests that they represent the same polypeptide fragment which has been differentially glycosylated. To assess the biological significance of these observations, CBG was incubated with either mononuclear cells or granulocytes obtained from patients with acute inflammation (sepsis) and from a normal volunteer. Only granulocytes from septic patients reduced the mol wt of CBG by about 5 kDa and destroyed its steroid-binding activity. Preincubation with A1-PI prevented this, which demonstrates that neutrophil elastase plays a key role in this event. These results suggest a physiological role for CBG in the delivery of cortisol to sites of inflammation.
在人体血液中，皮质醇由一种名为皮质类固醇结合球蛋白（CBG）的血浆蛋白运输。从CBG与α1-蛋白酶抑制剂（A1-PI）的一级结构比较可以预期，CBG可作为中性粒细胞弹性蛋白酶的底物。然而，与A1-PI不同的是，CBG不会改变这种酶的活性，而是在靠近其羧基末端的单个位置被其切割，这使其分子大小减少了5 kDa，同时释放出超过80%与CBG结合的皮质醇。弹性蛋白酶切割后可检测到三个小分子片段，对这些片段的碳水化合物分析表明，它们代表了同一多肽片段的不同糖基化形式。为了评估这些观察结果的生物学意义，将CBG与从急性炎症（脓毒症）患者和正常志愿者获得的单核细胞或粒细胞一起孵育。只有脓毒症患者的粒细胞使CBG的分子量降低了约5 kDa，并破坏了其类固醇结合活性。与A1-PI预孵育可防止这种情况发生，这表明中性粒细胞弹性蛋白酶在这一过程中起关键作用。这些结果提示CBG在将皮质醇输送到炎症部位方面具有生理作用。
