Inactivation of lung surfactant is characterized by increased conversion of heavy (H) to light (L) subtypes as identified on sucrose gradients. A protease(convertase) has been implicated as a factor responsible for this conversion during surface-cycling of natural surfactant.

We studied the effects of oxidants on the proportion of L to H (L/H) aggregates (by phospholipid analysis) after surface cycling for 24 h at 37°C of natural lung surfactant (NLS), Beractant (Ber), and KL4 surfactant containing synthetic peptide leucine/lysine. With these surfactants, oxidant exposure caused significant inhibition of minimum surface tensions to >20 mN/m. In all surfactants tested, the unoxidized form had L/H of 8-10%. In Ber the L/H with OCl- (1 mmol/l) was 23.1%, with ONOO- (2 mmol/l) 13.0%, and with Fenton reactants (30 mmol/l H202 + 0.065-0.65 mmol/l FeCl2)(F) 0.0%. In KL4 the L/H with OCl- was 29.1%, with ONOO- 14.1%, and with F 0.0%. In NLS, Ber and KL4 F generated an ultraheavy band with surface activity >20 mN/m.

Oxidative inactivation of surfactant causes increased L/H independent of convertase activity; however, it may be synergistic with protease effectsin vivo. F may inactivate surfactant by molecular mechanisms different from that of OCl- and ONOO-, such as oxidative effects on proteins or peptides. Supported by R.W. Johnson PRI.