Kallistatin, a novel human tissue kallikrein inhibitor: Levels in body fluids, blood cells, and tissues in health and disease
Kallistatin, a novel human tissue kallikrein inhibitor: Levels in body fluids, blood cells, and tissues in health and disease
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DOI：
10.1016/s0022-2143(96)90152-3
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发表时间：
1996-06-01
期刊：
影响因子：
--
通讯作者：
Chao, L
中科院分区：
文献类型：
--
作者：
Chao, JL;Schmaier, A;Chao, L
激肽释放酶抑制剂是一种新发现的组织激肽释放酶抑制剂。它与组织激肽释放酶结合强烈，但与其他丝氨酸蛋白酶如胰凝乳蛋白酶和弹性蛋白酶结合较弱。通过使用针对激肽抑制素的特异性单克隆抗体和多克隆抗体来表征人类疾病中激肽抑制素水平的组织分布和变化。用特异性酶联免疫吸附试验测定的血细胞、体液和组织中的激肽释放酶抑制剂抗原水平显示与纯化的激肽释放酶抑制剂平行的置换曲线，表明其免疫学特性。通过逆转录-聚合酶链反应，随后进行Southern印迹分析，鉴定了血小板、中性粒细胞、淋巴细胞、单核细胞、内皮细胞、肝细胞以及结肠癌和前列腺癌细胞中的激肽释放酶mRNA的表达。30名正常人血浆激肽释放酶抑制剂浓度为22.1 ± 3.5 μ g/ml，5名C1抑制剂缺乏症患者血浆激肽释放酶抑制剂浓度为21.1 ± 3.8 μ g/ml，A显著降低激肽释放酶抑制剂水平（7.2 ± 2.5 μ g/ml，P < 0.001），在9例肝病患者和10例脓毒症患者的血浆样本中观察到（7.7 +/- 3.5 μ g/ml，p < 0.001）。此外，10名口服避孕药的妇女（19.8 +/- 3.8 μ g/ml）和21名孕妇（14.9 +/- 3.3 μ g/ml）的激肽释放酶抑制剂水平显著低于健康个体。这些数据表明，激肽释放酶抑制剂存在于血浆中，主要在肝脏中产生，并且可以在脓毒症期间消耗。在败血症中食用它可能具有预防血压降低的保护作用。
Kallistatin, a human serine proteinase inhibitor, is a newly identified tissue kallikrein inhibitor. It binds strongly to tissue kallikrein but weakly to other serine proteinases such as chymotrypsin and elastase. The tissue distribution and changes in kallistatin levels in human diseases were characterized by using specific monoclonal and polyclonal antibodies against kallistatin. Kallistatin antigen levels in blood cells, fluids, and tissues measured with a specific enzyme-linked immunosorbent assay showed displacement curves that were parallel with those in purified kallistatin, indicating their immunologic identity. Expression of kallistatin mRNA in platelets, neutrophils, lymphocytes, monocytes, endothelial cells, hepatocytes, and colon and prostate carcinoma cells was identified by reverse transcription-polymerase chain reaction followed by Southern blot analysis. Plasma kallistatin concentration was 22.1 +/- 3.5 mu g/ml in 30 normal subjects and 21.1 +/- 3.8 mu g/ml in 5 patients with C1 inhibitor deficiency, A significantly reduced kallistatin level (7.2 +/- 2.5 mu g/ml, p < 0.001) was seen in plasma samples from 9 patients with liver disease and 10 patients with sepsis (7.7 +/- 3.5 mu g/ml, p < 0.001), Further, kallistatin levels in 10 women taking oral contraceptives (19.8 +/- 3.8 mu g/ml) and 21 pregnant women (14.9 +/- 3.3 mu g/ml) were significantly lower than those seen in healthy individuals. These data suggest that kallistatin is found in plasma, is produced mostly in the liver, and can be consumed during sepsis. Its consumption in sepsis may Indicate a protective role to prevent blood pressure lowering.