Vogelmeier C, Hubbard R C, Fells G A, Schnebli H P, Thompson R C, Fritz H, Crystal R G
Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
J Clin Invest. 1991 Feb;87(2):482-8. doi: 10.1172/JCI115021.
Secretory leukoprotease inhibitor (SLPI), a 12-kD nonglycosylated serine antiprotease with a high capacity for inhibiting neutrophil elastase (NE), is produced by cells of mucosal surfaces including the human lung. The molar concentrations of SLPI in total respiratory tract epithelial lining fluid (ELF) were 56 +/- 10% that of alpha 1-antitrypsin, suggesting SLPI may be more important for the anti-NE protection of the pulmonary epithelial surface than previously thought. However, evaluation demonstrated that SLPI in respiratory ELF was only one-third functional. Studies aerosolizing recombinant SLPI (rSLPI) to sheep demonstrated that in the short term, neither aerosolization and alveolar deposition nor the lavage procedure inactivated the SLPI molecule. In vitro studies with rSLPI demonstrated that exposure to oxidants did not modify the form of the molecule, while exposure to oxidants and NE caused the molecule to be cleaved from 12 to 8 kD. Consistent with this, evaluation of SLPI in lavage fluid of individuals with cystic fibrosis (a condition with oxidants and NE on the respiratory epithelium) showed that the SLPI was degraded. However, evaluation of SLPI in normal ELF by molecular sieve analysis and Western analysis demonstrated an intact 12-kD molecule, suggesting that the partial inactivation of SLPI in normals in vivo is not because it is complexed to NE or exposed to oxidants + NE. Together, these observations demonstrate that SLPI is present in large amounts in respiratory ELF, but since the majority of the SLPI is inactive, it likely does not play a significant role in protecting the normal respiratory epithelium, except perhaps in the upper airways where the levels of SLPI are the highest.
分泌型白细胞蛋白酶抑制剂（SLPI）是一种12千道尔顿的非糖基化丝氨酸抗蛋白酶，具有很强的抑制中性粒细胞弹性蛋白酶（NE）的能力，由包括人肺在内的黏膜表面细胞产生。在整个呼吸道上皮衬液（ELF）中，SLPI的摩尔浓度为α1-抗胰蛋白酶的56±10%，这表明SLPI对肺上皮表面的抗NE保护作用可能比之前认为的更为重要。然而，评估显示呼吸道ELF中的SLPI只有三分之一具有活性。对绵羊雾化重组SLPI（rSLPI）的研究表明，短期内，雾化和肺泡沉积以及灌洗过程都不会使SLPI分子失活。对rSLPI的体外研究表明，暴露于氧化剂不会改变分子的形式，而暴露于氧化剂和NE会导致分子从12千道尔顿裂解为8千道尔顿。与此一致的是，对囊性纤维化患者（一种呼吸道上皮存在氧化剂和NE的疾病）灌洗液中的SLPI进行评估发现，SLPI被降解。然而，通过分子筛分析和蛋白质免疫印迹分析对正常ELF中的SLPI进行评估，结果显示存在完整的12千道尔顿分子，这表明正常人体内SLPI的部分失活并非因为它与NE结合或暴露于氧化剂+NE。这些观察结果共同表明，SLPI大量存在于呼吸道ELF中，但由于大多数SLPI无活性，它可能在保护正常呼吸道上皮方面不起重要作用，也许在上呼吸道除外，因为那里SLPI的水平最高。
