Surfactant subtypes. In vitro conversion, in vivo function, and effects of serum proteins

Surfactant in the alveolar space can be separated into heavy and light subtypes by differential centrifugation or on isopyknic sucrose density gradients. The conversion from heavy subtypes to light subtypes occurs in vitro by surface-area cycling. However, the function of light subtypes made by cycling and substances that might influence in vitro conversion have not been evaluated. Therefore, we compared the in vivo function of the heavy and light subtypes isolated from rabbit surfactant and similar density fractions prepared in vitro by surface-area cycling. We then asked if serum, globulin, or albumin would alter the in vitro conversion. The function of surfactant fractions was studied in vivo by treating surfactant-deficient 27 d gestational age preterm rabbits with 50 mg/kg of heavy or light subtype surfactant. Dynamic compliance values and lung volumes from PV curve measurements showed that heavy subtypes had superior in vivo function compared with light subtypes independent of in vivo or in vitro sources (p < 0.01). Light subtypes prepared in vitro lost surfactant function and were similar to in vivo light forms. When serum proteins were added to the heavy subtype surfactant, the conversion rate from heavy to light subtypes was accelerated. Serum accelerated conversion more than globulin, and the serine proteinase inhibitor diisopropylfluorophosphate blocked the conversion. Albumin had no significant effect. The increased rate of conversion caused by serum identifies a new mechanism for surfactant inactivation that could occur with lung injuries associated with increased alveolar protein.