MONOCROTALINE ALTERS TYPE-II PNEUMOCYTE MORPHOLOGY AND POLYAMINE REGULATION

Lungs from monocrotaline (MCT)-treated rats exhibit altered polyamine metabolism and content. One of the prominent morphological abnormalities in MCT-treated lungs is a decrease in population density of type II pneumocytes. Against this background, the present study tested the hypothesis that failure to maintain normal population density of type II pneumocytes is associated with MCT-induced derangements in polyamine biosynthesis and/or transmembrane polyamine transport. After a 24-hr treatment, cultured type II pneumocytes exhibited numerous vacuoles at the highest dose of 3.2 mM MCT but not at the lower dose of 1.6 mM MCT. Intracellular spermidine content was significantly reduced at the highest dose of MCT. Relative to controls, the abundance of mRNA for both ornithine decarboxylase, and S-adenosylmethionine decarboxylase, key regulatory enzymes in polyamine synthesis, was not altered. However, the activities of both of these enzymes were dramatically reduced. Increased mRNA for the catabolic polyamine enzyme, spermine/spermidine-N-1-acetyltransferase (SAT), paralleled significant increases in SAT activity. MCT also caused a concentration-related inhibition of spermidine uptake in type II cells, characterized by a fourfold decrease in V-max with little change in K-m. These results show that MCT alters type II pneumocyte polyamine regulatory mechanisms and may help explain the decreased population density of type II pneumocytes in MCT-treated rats. (C) 1994 Academic Press, Inc.