Effect of fibrinogen degradation products and lung ground substance on surfactant function.
Acute lung injury syndromes have many characteristics including protein-rich alveolar edema, hyaline membranes, and abnormal surface tension at the alveolar air-liquid interface. Increased surface tension can occur because of a relative surfactant deficiency and/or dysfunction. It has been previously demonstrated that surfactant dysfunction occurs when plasma protein inhibitors leak into the alveolar space during the induction of the lung injury and edema formation. The present study investigated whether inhibitors that would be generated during the stage of repair from lung injury could impair surfactant function. We determined whether fibrinogen degradation products (FDP) which would be released during lysis of the fibrin(ogen)-containing alveolar exudate and hyaline membranes, and components of the lungs' ground substance could inhibit the in vitro function of a lipid extract surfactant preparation. FDP were prepared by incubating human fibrinogen with plasmin or neutrophil elastase for 4 min to 60 h and were characterized by SDS-PAGE. Early (fragment X and Y) and late (fragment D and E) plasmin-derived FDP (MW greater than 40,000) inhibited surfactant function as assessed by a bubble surfactometer. The early elastase-derived FDP also inhibited surfactant, but the later and much smaller fragments (MW less than 15,000) did not affect surfactant function. Laminin also inhibited surfactant in a dose-dependent manner. Neither hyaluronic acid nor heparan sulfate affected surfactant performance in vitro. We conclude that plasmin-induced lysis of intraalveolar fibrinogen and hyaline membranes will result in prolonged generation (i.e. days) of surfactant inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)
O'Brodovich
H M
HM
Department of Pediatrics, Hospital for Sick Children, Toronto, Ont., Canada.
Weitz
J I
JI
Possmayer
F
F
D000818:Animals; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005338:Fibrin Fibrinogen Degradation Products / Q000494:pharmacology*; D005341:Fibrinolysin / Q000494:pharmacology; D006497:Heparan Sulfate / Q000494:pharmacology; D006801:Humans; D006819:Hyaline Membrane Disease / Q000503:physiopathology*; D006820:Hyaluronic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D007231:Infant, Newborn; D007797:Laminin / Q000494:pharmacology; D008168:Lung / Q000503:physiopathology; D010196:Pancreatic Elastase / Q000494:pharmacology; D011663:Pulmonary Surfactants / Q000502:physiology*; D012128:Respiratory Distress Syndrome / Q000503:physiopathology*; D013500:Surface Tension
D005338:Fibrin Fibrinogen Degradation Products; D005341:Fibrinolysin; D006497:Heparan Sulfate; D006820:Hyaluronic Acid; D007797:Laminin; D010196:Pancreatic Elastase; D011663:Pulmonary Surfactants