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)