This research studies the biophysical surface activity of synthetic
phospholipids combined in vitro with purified lung
surfactant apoprotein, having an Mr of 6000. Hydrophobic
surfactant-associated
protein (SAP-6) was delipidated and purified from both bovine and canine lung lavage, and was combined in vitro with a synthetic
phospholipid mixture (SM) of similar composition to natural lung
surfactant phospholipids. SM
phospholipids were also combined and studied biophysically with another purified
surfactant-associated
protein, SAP-35. The biophysical activity of synthetic
phospholipid-
apoprotein combinants was assessed by measurements of adsorption facility and dynamic surface tension lowering ability at 37 degrees C. The SM-SAP-6 combinants had adsorption facility equivalent to natural lung
surfactant, and to the
surfactant extract preparations CLSE and
surfactant-TA used in exogenous
surfactant replacement
therapy for the
neonatal Respiratory Distress Syndrome (RDS). The synthetic phospholipid-SAP-6 combinants also lowered surface tension to less than 1 dyne/cm under dynamic compression in an oscillating bubble apparatus at concentrations as low as 0.5 mg
phospholipid/ml. A striking finding was that this excellent dynamic surface activity was preserved as SAP-6 composition was reduced to values as low as 5 micrograms/5 mg SM
phospholipid (0.1% SAP-6
protein), an order of magnitude less than the 1%
protein content of CLSE and
surfactant-TA. Mixtures of SM
phospholipids plus SAP-35, the major
surfactant glycoprotein, had significantly lower biophysical activity, which did not approach that of a functional lung
surfactant. These results suggest that synthetic exogenous
surfactants of potential utility for replacement
therapy in RDS can be formulated by combining synthetic
phospholipids in vitro with specifically purified, hydrophobic
surfactant-associated
protein, SAP-6.