The influence of pH on surface properties of lung surfactants.

Protein-lipid interactions at air-liquid interfaces are dependent on electrostatic charges, cations, anions, distribution of protons, and surface potential, which are influenced by pH changes. All of these factors may affect lung surfactant function. To verify the pH dependence of surface activity of pulmonary surfactant, we studied the in vitro effects of pH and Ca2+ on the surface tension-lowering abilities of various surfactants in an oscillating bubble surfactometer. Surface tension measurements were made of mixtures at known pHs or after the replacement of the subphase fluid of surfactant films with buffered saline at various pH values. At the pH range 4.0-7.0, the average equilibrium surface tension (EST)/minimum surface tension (MST) for natural surfactants human amniotic fluid and natural lung surfactant from rabbit lung lavage was 24/2 mN/m. At the same pH range, Exosurf and phospholipids alone had an EST/MST of 44/25 and 44/12 mN/m, respectively. Survanta (SUR) containing SP-B and SP-C and a phospholipid surfactant (KL4) containing a leucine/lysine peptide had an EST/MST of 29/5 and 36/3, respectively. Alkalinization of the subphase (pH > 7.4) significantly decreased the surface tension-lowering ability of SUR (P < 0.01) and to a lesser extent that of KL4 surfactant (P < 0.05), but natural lung surfactants were not significantly affected over a pH range of 3-7.5. These data demonstrate that natural surfactants maintain their optimal surface activities over a broader pH range than do the commercial products because of a lack of SP-A. Careful monitoring of the pH for optimal surface activity is recommended when evaluating surfactant function and the effects of specific inhibitors on this function.