Abstract

Pulmonary surfactant is a mixture of lipids and proteins, essential to reduce the surface tension at the air-liquid interface in the alveoli of mammalian lungs and so stabilizing the respiratory surface. Lack of an operative surfactant is associated with severe respiratory pathologies and supplementation with exogenous surfactants has been widely approached as a potential therapeutic intervention. However, the optimal lipid and protein composition of exogenous surfactants has not been properly established, and clinical surfactants currently in use differ substantially in terms of their lipid and protein moieties. In the present study we have compared the surface activity of native SP-B and /or SP-C, purified from porcine lungs, in the Captive Bubble Surfactometer (CBS), once reconstituted into two different synthetic lipid mixtures: DPPC/POPC/POPG/Chol (50:25:15:10) (lipidS), a mixture mimicking lipid composition in natural surfactant, and DPPC/POPG/Palmitic Acid (68:22:9) (lipidTA), a system widely used as a basis for clinical surfactants. We found similar equilibrium surface tensions after 5 min of adsorption of all the samples, regardless the protein and lipid system, although SP-B exhibited somehow slower initial adsorption in lipidTA. Significant differences were found in SP-B activity under quasi static compression-expansion cycling for the two lipid systems tested. In lipidTA, SP-B allowed reaching tensions near 2mN/m, whereas in lipidS surface tension did not fall below 20mN/m. However, SP-B-containing samples produced similarly low tensions, within the two lipid compositions, once cycled dynamically at physiologically relevant compression-expansion rates. Analysis of film stability under mechanical perturbations showed that SP-B introduces a significant resistance of the films to relaxation, which is particularly remarkable in lipidS samples. This stability was maximal in the simultaneous presence of SP-B and SP-C.

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