The role of alpha 1-antitrypsin in the control of extracellular surfactant metabolism.
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.
Gross
N J
NJ
Medical Service, Hines Veterans Affairs Hospital, Illinois 60141.
Bublys
V
V
D'Anza
J
J
Brown
C L
CL
D000818:Animals; D002499:Centrifugation, Density Gradient; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D005990:Glycerol / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D051379:Mice; D011650:Pulmonary Alveoli / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000302:isolation & purification / Q000378:metabolism*; D007507:Therapeutic Irrigation; D014132:Trachea / Q000187:drug effects; D014316:Tritium; D000515:alpha 1-Antitrypsin / Q000008:administration & dosage / Q000502:physiology*
D011663:Pulmonary Surfactants; D000515:alpha 1-Antitrypsin; D014316:Tritium; D005990:Glycerol