APOPROTEIN-BASED SYNTHETIC SURFACTANTS INHIBIT PLASMIC CLEAVAGE OF FIBRINOGEN IN-VITRO

Fibrinogen (Fbg) leakage and intra-alveolar fibrin accumulation are co mmonly noticed in adult respiratory distress syndrome and interstitial lung diseases. Activation of the extrinsic coagulation pathway and el evation of antiplasmin- and plasminogen-activator inhibitor levels are assumed to favor alveolar clot formation and to inhibit fibrinolysis under these conditions. We investigated the influence of synthetic sur factants on the plasmic cleavage of fibrinogen in vitro. Fibrinogenoly sis was quantified by sodium dodecyl sulfate-polyacrylamide gel electr ophoresis with densitometric evaluation and fragment E enzyme-linked i mmunosorbent assay. A synthetic phospholipid mixture (PLM) (dipalmitoy l-DL-alpha-phosphatidylcholine: L-alpha-phosphatidyl-DL-glycerol: palm itic acid 68.5:22.5:9) caused a dose-dependent inhibition of fibrinoge nolysis in a concentration range between 0.1 and 2 mg/ml. This inhibit ory capacity was markedly amplified upon reconstitution of PLM with na tural and recombinant surfactant protein (SP)-C as well as natural SP- B. Natural SP-A and recombinant SP-A were far less effective in this r espect. In the absence of phospholipids, the hydrophobic apoproteins r evealed only moderate plasmin inhibitory capacity (recombinant SP-C > natural SP-C and SP-B). Natural calf lung surfactant extract displayed comparable inhibitory capacity on plasmic Fbg cleavage as PLM. We con clude that hydrophobic surfactant material may suppress plasmin activi ty and thus may contribute to the finding of delayed alveolar fibrin c learance in inflammatory lung diseases with Fbg leakage.