Effects of activated polymorphonuclear leukocytes upon pulmonary surfactant in vitro.
Current evidence suggests that products of activated inflammatory cells cause or contribute to the acute lung injury of the adult respiratory distress syndrome (ARDS). To assess the possibility that these products may impair surfactant function during ARDS, we exposed surfactant in vitro to polymorphonuclear leukocytes (PMN) activated by phorbol myristate acetate and to the oxidant-producing pair ferric chloride/ascorbate (FeCl3/ASC). After incubation of surfactant with 8 to 32 x 10(6) activated PMN for 1 to 4 h or with FeCl3/ASC for 16 h, its isopycnic density (d), minimum surface tension (gamma min), time course of adsorption, compressibility (SC), and stability index (SI) were determined. We found progressive decreases of d, adsorption, and SI and progressive increases of gamma min and SC after exposure to activated PMN in increasing numbers or for longer time periods. Superoxide dismutase completely inhibited all of these effects except the decreased adsorption, which it did not significantly inhibit. Similar changes in all of these parameters occurred after exposure of surfactant to FeCl3/ASC. Polyacrylamide gel electrophoresis of surfactant after exposure to activated PMN showed a decrease of the major apoprotein that progressed with exposure time and was associated with the appearance of several bands with both lower and higher molecular weights than that of the apoprotein. The data show that activated PMN are capable of impairing surfactant function in vitro and of degrading the major apoprotein. They suggest that the effects upon d, gamma min, SC, and SI are mediated largely if not exclusively by oxidant radicals. While oxidants may contribute to delayed adsorption, proteolysis appears to play the principal role in this effect.
Ryan
S F
SF
Department of Pathology, St. Luke's-Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, New York, NY 10025.
Ghassibi
Y
Y
Liau
D F
DF
D000327:Adsorption; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D002500:Centrifugation, Isopycnic; D002712:Chlorides; D004285:Dogs; D004591:Electrophoresis, Polyacrylamide Gel; D005290:Ferric Compounds / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008213:Lymphocyte Activation; D008297:Male; D009504:Neutrophils / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000737:chemistry* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013500:Surface Tension; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002712:Chlorides; D005290:Ferric Compounds; D011663:Pulmonary Surfactants; D013482:Superoxide Dismutase; D013755:Tetradecanoylphorbol Acetate; D001205:Ascorbic Acid; C024555:ferric chloride