Inhibition of surfactant subtype convertase in radiation model of adult respiratory distress syndrome.
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)
Gross
N J
NJ
Medical Service, Hines Veterans Administration Hospital 60141.
D000818:Animals; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D011650:Pulmonary Alveoli / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000145:classification / Q000302:isolation & purification / Q000378:metabolism*; D011833:Radiation Injuries, Experimental / Q000378:metabolism*; D012016:Reference Values; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism*; D007507:Therapeutic Irrigation
D011663:Pulmonary Surfactants; D012697:Serine Endopeptidases; C068328:surfactant subtype convertase