Clot-embedded natural surfactant: kinetics of fibrinolysis and surface activity.
Polymerization of fibrin in the presence of pulmonary surfactant was recently noted to induce incorporation of phospholipids into the insoluble clot material, thereby effecting severe loss of surface activity (W. Seeger, A. Elssner, A. Günther, H.-J. Krämer, and H. O. Kalinowski. Am. J. Respir. Cell Mol. Biol. 9: 213-220, 1993). In the present study, we investigated the influence of such incorporation of calf lung surfactant extract (CLSE) on the enzymatic cleavage of the fibrin network with the use of plasmin, trypsin, or elastase. Employing a fibrin-plate assay, the proteolytic release of radioactivity originating from 125I-labeled fibrinogen was assessed, and the pattern of split products was characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis technique. Surface activity of CLSE was measured in the pulsating bubble surfactometer. When incorporated into the fibrin clot, CLSE inhibited the cleavage of fibrin by all proteases in a dose-dependent manner without affecting the profile of scission products. Inhibition of plasmin-induced clot lysis was also noted on incorporation of CLSE into clotted plasma and on incorporation of dipalmitoylphosphatidylcholine into fibrin polymers. In contrast, corresponding concentrations of CLSE added to the incubation medium after preformation of the fibrin matrix did not substantially influence the kinetics of fibrinolysis. CLSE incorporation into the nascent fibrin clot resulted in complete loss of surface activity, but adsorption and surface tension-lowering properties were largely restored by subsequent plasmic clot lysis. Arising fibrin split products were shown to display similar inhibitory strength on CLSE surface activity compared with fibrinogen split products.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Internal Medicine, Justus Liebig University, Giessen, Germany.
A
A
Günther
M
M
Kalinowski
A
A
Elssner
W
W
Seeger
D000818:Animals; D001769:Blood / Q000378:metabolism*; D001777:Blood Coagulation; D002417:Cattle; D005337:Fibrin / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism; D005342:Fibrinolysis; D007700:Kinetics; D010196:Pancreatic Elastase / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000378:metabolism*; D013499:Surface Properties; D014357:Trypsin / Q000378:metabolism
D011663:Pulmonary Surfactants; D005337:Fibrin; D010447:Peptide Hydrolases; D010196:Pancreatic Elastase; D014357:Trypsin; D005341:Fibrinolysin