A protein from airways of premature lambs that inhibits surfactant function

A protein that interfered with surfactant function was isolated from the alveolar washes of prematurely delivered and ventilated lambs. This inhibitor was recovered following sequential precipitation with polyethylene glycol, Affi-Gel Blue, and diethylaminoethyl (DEAE) cellulose chromatography as a protein of approximately 110,000 mol wt. Compared to surfactant alone or surfactant and bovine serum albumin, the purified inhibitor increased the time required for surfactant to spread, increased both maximal and minimal surface tensions, increased the percent surface area that had to be compressed to reach a minimum surface tension of less than 15 dyn/cm, and delayed the surface adsorption of surfactant. The effect of inhibitor on the minimum surface tensions of surfactant solutions was inversely related to surfactant concentration. A radioimmunoassay was used to estimate that approximately 10% of the protein from plasma of premature lambs and alveolar washes after 4 h of ventilation was inhibitory. Following the simultaneous intravascular injection of labeled inhibitor and bovine serum albumin, about 4% of the radioactivity associated with both proteins was recovered in alveolar washes and 6% was associated with lung tissue after alveolar wash. This large proportionate leakage of both proteins did not occur in other tissues. The inhibitor affected multiple measurements of surfactant function in vitro and its presence may contribute to a surfactant deficiency state in the immature lung.