Vogelmeier C, Buhl R, Hoyt R F, Wilson E, Fells G A, Hubbard R C, Schnebli H P, Thompson R C, Crystal R G
Section of Laboratory Animal Medicine and Surgery, National Heart Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
J Appl Physiol (1985). 1990 Nov;69(5):1843-8. doi: 10.1152/jappl.1990.69.5.1843.
In a variety of lung diseases the respiratory epithelial surface must contend with an increased burden of neutrophil elastase (NE). One candidate for augmenting epithelial anti-NE protection is the secretory leukoprotease inhibitor (SLPI). In vitro evaluation demonstrated that 96 +/- 1% of the recombinant SLPI (rSLPI) molecules were capable of inhibiting NE, with an association rate constant of 7.1 +/- 0.1 X 10(6) M-1.s-1. Evaluation of rSLPI after in vitro and in vivo aerosolization showed that aerosolization did not alter rSLPI. Aerosolization of a single dose of 50 mg rSLPI to sheep resulted in a fourfold increase of the anti-NE capacity in epithelial lining fluid (ELF) at 3 h, with a half-life in ELF of 12 h. After aerosolization some rSLPI appeared in lung lymph. Simultaneous aerosolization of rSLPI and recombinant alpha 1-antitrypsin (rAAT) demonstrated a molar ratio of the concentration in lymph to the concentration in ELF 3 h after the aerosol eightfold higher for rAAT than for rSLPI. Overall, these observations demonstrate that it is feasible to use aerosolized rSLPI to directly augment the anti-NE capacity of the lung, particularly on the pulmonary epithelial surface.
在多种肺部疾病中，呼吸道上皮表面必须应对中性粒细胞弹性蛋白酶（NE）负荷的增加。增强上皮抗NE保护作用的一个候选物质是分泌型白细胞蛋白酶抑制剂（SLPI）。体外评估表明，96±1%的重组SLPI（rSLPI）分子能够抑制NE，其结合速率常数为7.1±0.1×10⁶ M⁻¹·s⁻¹。对体外和体内雾化后的rSLPI进行评估表明，雾化不会改变rSLPI。对绵羊单次雾化50 mg rSLPI后，3小时时上皮衬液（ELF）中的抗NE能力增加了四倍，在ELF中的半衰期为12小时。雾化后，一些rSLPI出现在肺淋巴中。同时雾化rSLPI和重组α1-抗胰蛋白酶（rAAT）表明，雾化8小时后3小时时，淋巴中浓度与ELF中浓度的摩尔比，rAAT比rSLPI高八倍。总体而言，这些观察结果表明，使用雾化的rSLPI直接增强肺部尤其是肺上皮表面的抗NE能力是可行的。
