AJP - Lung Cellular and Molecular Physiology, Vol 268, Issue 3 438-L445, Copyright © 1995 by American Physiological Society
The role of alpha 1-antitrypsin in the control of extracellular surfactant metabolism
N. J. Gross, V. Bublys, J. D'Anza and C. L. Brown
Medical Service, Hines Veterans Affairs Hospital, Illinois 60141.
Alveolar surfactant exists in several structural forms that are believed to
be secular products of the secreted form, lamellar bodies. The conversion
of tubular myelin to the small vesicular form appears to require the action
of a novel serine protease, surfactant convertase. As the in vitro activity
of this enzyme is quite sensitive to inhibition by the serine protease
inhibitor alpha 1-antitrypsin, a normal constituent of the alveolar fluid
lining layer, we explored the possibility that the alveolar level of alpha
1-antitrypsin might affect the rate of subtype conversion in vivo. When the
alveolar alpha 1-antitrypsin level was augmented by tracheal instillation
of exogenous alpha 1-antitrypsin, the newly synthesized surfactant
phospholipids of spontaneously breathing mice accumulated in the heavy
subtype, and virtually none was found in the light subtype form up to 72 h
later. An in vivo turnover study suggested that when the alveolar alpha
1-antitrypsin level was raised by the same means, the flux of surfactant
through the light (small vesicular) compartment was virtually shut off,
despite the availability of abundant amounts of its precursor, heavy
subtype (tubular myelin). Finally, mouse lungs that were lavaged to remove
resident surfactant and mechanically ventilated for 1-5 h released
surfactant that progressed through heavy and light subtype compartments as
in vivo. But in mice whose lung alpha 1-antitrypsin might affect the
metabolism of alveolar surfactant in addition to its well-known role in
lung defense.
