title: Apoprotein-based synthetic surfactants inhibit plasmic cleavage of fibrinogen in vitro.
abstract: Fibrinogen (Fbg) leakage and intra-alveolar fibrin accumulation are commonly noticed in adult respiratory distress syndrome and interstitial lung diseases. Activation of the extrinsic coagulation pathway and elevation 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 surfactants on the plasmic cleavage of fibrinogen in vitro. Fibrinogenolysis was quantified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis with densitometric evaluation and fragment E enzyme-linked immunosorbent assay. A synthetic phospholipid mixture (PLM) (dipalmitoyl-DL-alpha-phosphatidylcholine:L-alpha-phosphatidyl-DL-gly cer ol: palmitic acid 68.5:22.5:9) caused a dose-dependent inhibition of fibrinogenolysis in a concentration range between 0.1 and 2 mg/ml. This inhibitory capacity was markedly amplified upon reconstitution of PLM with natural 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 respect. In the absence of phospholipids, the hydrophobic apoproteins revealed 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 conclude that hydrophobic surfactant material may suppress plasmin activity and thus may contribute to the finding of delayed alveolar fibrin clearance in inflammatory lung diseases with Fbg leakage.
authors.affiliation: Department of Internal Medicine, Justus Liebig University, Giessen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Günther
authors.forename: H
authors.initials: H
authors.lastname: Bleyl
authors.forename: W
authors.initials: W
authors.lastname: Seeger
mesh_terms: D000818:Animals; D001059:Apoproteins / Q000737:chemistry*; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005340:Fibrinogen / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D010743:Phospholipids / Q000494:pharmacology; D011663:Pulmonary Surfactants / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D001059:Apoproteins; D010743:Phospholipids; D011663:Pulmonary Surfactants; D005340:Fibrinogen; D005341:Fibrinolysin