The accompanying paper [Am. J. Physiol. 260 (Lung Cell. Mol. Physiol. 4): L302-L310, 1991] showed that in the
radiation pneumonitis model of
adult respiratory distress syndrome (ARDS) there was an excess of the proximate, higher buoyant density subtypes of alveolar
surfactant, and a decrease in the light buoyant density form. Because the
surfactant subtypes normally evolve from the former to the latter a delay in the alveolar metabolism of
surfactant could explain this disproportion. Three possible mechanisms of a delay in
surfactant metabolism in
radiation pneumonitis were explored using an in vitro model of
surfactant subtype metabolism called "cycling". The first was that the
surfactant of mice with
radiation pneumonitis was intrinsically less capable of conversion to the light subtype. It was found, however, that the proximate forms of
surfactant of mice with
radiation pneumonitis were as capable of generating light subtype as those of control mice. The second was that there was a deficit in the
serine protease activity, called "convertase", that mediates the conversion. But it was found that lungs of mice with
radiation pneumonitis released convertase activity to the same extent as control lungs. The third was that an inhibitor of convertase activity was present in the alveoli. It was found that the alveolar lavage fluid of mice with
radiation pneumonitis inhibited the conversion of exogenous
surfactant by exogenous convertase. Moreover, it contained an 18-fold excess of
antiprotease activity. The present data are interpreted as suggesting that an inhibitor in the alveolar space is responsible for the delay in
surfactant subtype metabolism in
radiation pneumonitis, resulting in the disproportion of
surfactant subtypes in
radiation pneumonitis.(ABSTRACT TRUNCATED AT 250 WORDS)