Pratt C W, Roche P A, Pizzo S V
Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710.
Arch Biochem Biophys. 1987 Nov 1;258(2):591-9. doi: 10.1016/0003-9861(87)90381-x.
The plasma clearance of neutrophil elastase, plasmin, and their complexes with human inter-alpha-trypsin inhibitor (I alpha I) was examined in mice, and the distribution of the proteinases among the plasma proteinase inhibitors was quantified in mixtures of purified inhibitors, in human or murine plasma, and in murine plasma following injection of purified proteins. The results demonstrate that I alpha I acts as a shuttle by transferring proteinases to other plasma proteinase inhibitors for clearance, and that I alpha I modulates the distribution of proteinase among inhibitors. The clearance of I alpha I-elastase involved transfer of proteinase to alpha 2-macroglobulin and alpha 1-proteinase inhibitor. The partition of elastase between these inhibitors was altered by I alpha I to favor formation of alpha 2-macroglobulin-elastase complexes. The clearance of I alpha I-plasmin involved transfer of plasmin to alpha 2-macroglobulin and alpha 2-plasmin inhibitor. Results of distribution studies suggest that plasmin binds to endothelium in vivo and reacts with I alpha I before transfer to alpha 2-macroglobulin and alpha 2-plasmin inhibitor. Evidence for this sequence of events includes observations that plasmin in complex with I alpha I cleared faster than free plasmin, that plasma obtained after injection of plasmin contained a complex identified as I alpha I-plasmin, and that a murine I alpha I-plasmin complex remained intact following injection into mice. Plasmin initially in complex with I alpha I more readily associated with alpha 2-plasmin inhibitor than did free plasmin.
在小鼠中检测了中性粒细胞弹性蛋白酶、纤溶酶及其与人α-胰蛋白酶抑制剂（IαI）复合物的血浆清除率，并在纯化抑制剂混合物、人或鼠血浆以及注射纯化蛋白后的鼠血浆中，对蛋白酶在血浆蛋白酶抑制剂中的分布进行了定量分析。结果表明，IαI通过将蛋白酶转移至其他血浆蛋白酶抑制剂进行清除，从而起到穿梭作用，并且IαI调节蛋白酶在抑制剂之间的分布。IαI-弹性蛋白酶的清除涉及蛋白酶向α2-巨球蛋白和α1-蛋白酶抑制剂的转移。IαI改变了弹性蛋白酶在这些抑制剂之间的分配，有利于形成α2-巨球蛋白-弹性蛋白酶复合物。IαI-纤溶酶的清除涉及纤溶酶向α2-巨球蛋白和α2-纤溶酶抑制剂的转移。分布研究结果表明，纤溶酶在体内与内皮细胞结合，并在转移至α2-巨球蛋白和α2-纤溶酶抑制剂之前与IαI发生反应。这一系列事件的证据包括以下观察结果：与IαI结合的纤溶酶比游离纤溶酶清除得更快；注射纤溶酶后获得的血浆中含有一种鉴定为IαI-纤溶酶的复合物；将小鼠IαI-纤溶酶复合物注射到小鼠体内后仍保持完整。最初与IαI结合的纤溶酶比游离纤溶酶更容易与α2-纤溶酶抑制剂结合。
