Tschesche H, Zölzer V, Triebel S, Bartsch S
Department of Biochemistry, Faculty of Chemistry, University of Bielefeld, Germany.
Eur J Biochem. 2001 Apr;268(7):1918-28. doi: 10.1046/j.1432-1327.2001.02066.x.
The human neutrophil lipocalin (HNL), a member of the large family of lipocalins that exhibit various physiological functions, is coexpressed in granulocytes with progelatinase B (MMP-9). Part of it is covalently bound to the proenzyme and therefore may play a possible role in the activation process of promatrix metalloproteinases. We now report that HNL is able to accelerate the direct activation of promatrix metalloproteinases slightly. A significant enhancement of the activity could be demonstrated for the HgCl2- and the plasma kallikrein-induced activation of all three secretory forms of proMMP-9 and of proMMP-8. The same activating effects were exerted by HNL isolated from granulocytes as well as by the recombinant forms expressed by the yeast Pichia pastoris or by Escherichia coli. This demonstrates that the carbohydrate moiety is not essential for the biological activity of HNL. Activation and activity enhancement are obviously mediated by entrapping the remaining N-terminal sequence residues of the partially truncated proenzyme into the hydrophobic binding pocket of the HNL. In conclusion these results document that HNL can exert an enzyme-activating effect in the regulation of inflammatory and pathophysiological responses of granulocytes in the physiological activation of MMPs that have been subject to limited proteolytic processing.
人嗜中性粒细胞脂质运载蛋白（HNL）是具有多种生理功能的脂质运载蛋白大家族的成员之一，它与前明胶酶B（MMP - 9）在粒细胞中共表达。其一部分与酶原共价结合，因此可能在基质金属蛋白酶原的激活过程中发挥作用。我们现在报告，HNL能够略微加速基质金属蛋白酶原的直接激活。对于HgCl₂和血浆激肽释放酶诱导的三种分泌形式的proMMP - 9和proMMP - 8的激活，其活性有显著增强。从粒细胞中分离出的HNL以及由酵母毕赤酵母或大肠杆菌表达的重组形式都具有相同的激活作用。这表明碳水化合物部分对于HNL的生物活性并非必需。激活和活性增强显然是通过将部分截短的酶原的剩余N端序列残基截留在HNL的疏水结合口袋中实现的。总之，这些结果证明，在对已经经历有限蛋白水解加工的MMPs进行生理激活过程中，HNL在粒细胞的炎症和病理生理反应调节中可发挥酶激活作用。
