title: [A coagulative type of pulmonary surfactant depletion--a mechanism of damage to the pulmonary surfactant system].
abstract: Plasma proteins, in particular fibrinogen and its degradation products leaking into air spaces in various forms of lung injuries, can adversely affect surfactant function. Two types of interaction of pulmonary surfactant with plasma proteins have been described: (1) a reversible type of interaction of surfactant with plasma proteins, and (2) a coagulative type of surfactant inactivation. The physiological significance of the latter mode of surfactant inactivation remains controversial. The purpose of this study was to determine the relative importance of these two modes of surfactant inactivation in an alveolar model. Surfactant-fibrinogen mixtures were prepared by adding fibrinogen at various concentrations to a standard preparation of surfactant-TA (suspended in Tris buffered saline at the final concentration of 1.25 mg/ml). To one of the mixtures were added caCl2 and thrombin, and the resulting fibrin clot was removed from the mixture by passing through polyethylene telephthalate filter. The surface activity of surfactant-TA suspension and the mixtures of surfactant-TA and fibrinogen before and after fibrin formation was examined during adsorption and dynamic compression using a pulsating bubble surfactometer. The concentrations of total phospholipid and surfactant-associated proteins (SP-B and SP-C) were also measured in these samples. Similar studies were performed with natural surfactant and dipalmitoylphosphatidylcholine (DPPC). Retarded adsorption of surfactant-TA and an increased minimum surface tension were observed in fibrinogen concentrations exceeding 2(-5) mg/ml. The inhibitory effect of fibrinogen on surfactant function reversed completely by 10-min after dynamic bubble pulsations. The magnitude of retarded adsorption and a lessening the ability to lower the minimum surface tension during dynamic bubble compression were significantly greater in the surfactant-fibrinogen mixtures after removal of the fibrin clots than in those before fibrin formation in fibrinogen concentrations exceeding 2(-3) mg/ml. More than 90% of both phospholipid and SP -B, C of surfactant-TA was incorporated into the fibrin clot in fibrinogen concentrations of > 2(-3) mg/ml. Similar results were obtained with natural surfactant or DPPC. At a fixed fibrinogen concentration of 2 mg/ml the fibrin clot removal was accompanied by a 90% loss of surfactant-TA in its concentration range of 1.25-40 mg/ml. Scanning electron microscopic examinations showed that numerous particles of surfactant-TA were seen embedded in fibrin network. The results of this study suggest that the coagulative type of pulmonary surfactant depletion may be more important than the reversible type of pulmonary surfactant inactivation by fibrinogen.
authors.affiliation: Department of Pediatrics, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Koga
mesh_terms: D005337:Fibrin / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D010743:Phospholipids / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000172:deficiency* / Q000378:metabolism; D012131:Respiratory Insufficiency / Q000209:etiology / Q000378:metabolism
chemical_list: D010743:Phospholipids; D011663:Pulmonary Surfactants; D005337:Fibrin; D005340:Fibrinogen