Journal of Applied Physiology AJP: Advances in Physiology Education
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J Appl Physiol 69: 1843-1848, 1990;
8750-7587/90 $5.00
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Journal of Applied Physiology, Vol 69, Issue 5 1843-1848, Copyright © 1990 by American Physiological Society

ARTICLES

Aerosolization of recombinant SLPI to augment antineutrophil elastase protection of pulmonary epithelium

C. Vogelmeier, R. Buhl, R. F. Hoyt, E. Wilson, G. A. Fells, R. C. Hubbard, H. P. Schnebli, R. C. Thompson and R. G. Crystal
Section of Laboratory Animal Medicine and Surgery, National Heart Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.

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.


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