LUNG SURFACTANT PHOSPHOLIPIDS ASSOCIATE WITH POLYMERIZING FIBRIN - LOSS OF SURFACE-ACTIVITY

Intraalveolar fibrin formation is a hallmark of many acute and chronic lung inflammatory processes. We investigated the influence of fibrin polymerization on biochemical and biophysical properties of a calf lung surfactant extract (CLSE) used for therapy of neonatal distress syndrome. Thrombin-induced coagulation of human fibrinogen (range, 0.04 to 4 mg/ml) in the presence of CLSE (2 mg/ml phospholipids) resulted in progressive loss of surface tension-lowering properties and adsorption facilities of this surfactant preparation; the CLSE-inhibitory capacity of desAABB-fibrin surpassed that of fibrinogen by more than two orders of magnitude. In parallel with the loss of surface activity, association of the predominant surfactant phospholipid dipalmitoylphosphatidylcholine (DPPC) (C-14-labeled, admixed to 2 mg/ml CLSE) with polymerizing desAABB-fibrin occurred. A volume of 0.3 mg/ml insoluble fibrin effected a almost-equal-to 50% loss, and 0.6 mg/ml a > 90% loss, of DPPC from the aqueous phase. Dioleoylphosphatidylcholine, dipahnitoylphosphatidic acid, stearic acid, palmitic acid, and arachidonic acid, admixed to CLSE as labeled compounds, as well as total CLSE phospholipids were retained in polymerizing desAABB-fibrin with dose-effect curves superimposable to that of DPPC; no fibrin association was noted for C-14-glycerol-3-phosphate. Polymerizing desAA-fibrin, generated by incubation of CLSE-fibrinogen mixtures with arvin, captured DPPC and resulted in loss of surface properties at even lower concentrations, compared with desAABB-fibrin. In contrast, CLSE incubation with preformed desAABB- and desAA-fibrin polymers did not cause substantial phospholipid coupling with the clot material or loss of surface properties. Microtiter plate-immobilized fibrinogen and desAABB- and desAA-fibrinomonomers did not bind CLSE phospholipids enriched with C-14-DPPC. Soluble desAABB- and desAA-fibrinmonomers, generated in the presence of GLY-PRO-ARG-PRO, did not exhibit surfactant-inhibitory properties different from those of fibrinogen (minimum inhibitory concentrations > 12 mg/ml, as assessed on 2 mg/ml CLSE). We conclude that surfactant phospholipids and fatty acids strongly bind to polymerizing fibrin, but not to fibrinogen and fibrinmonomer, with concomitant loss of surface activity.