Studies on Changes in Pulmonary Surfactant in Pathological States of the Lung. 1. Acute Lung Injury Induced by N-nitroso-N-methylurethane : ARDS Like Model

The levels of surfactant protein （SP）-A, SP-B and SP-D were studied in bron-choalveolar lavage （BAL）-subfractions and lamellar body （LB） subfractions of rats with acute lung injury due to subcutaneous injection of N-nitroso-N-methylurethane （NMU, 4.0 mg/kg of body weight）. NMU-injected or saline-injected rats were sacrificed on day 2, day 4 and day 7, and BAL and LB were obtained. The BAL was divided into two subfractions by two different methods, i. e, alv I and alv 2 fractions as defined by Nicholas et al, and LA （large aggregates） and SA （small aggregates） fractions according to Jobe et al. The LB was divided into two subfractions, IbA and lbB fractions according to Nicholas et al. These BAL-subfractions and LB subfractions were anal-yzed for total protein, total phospholipid and surfactant proteins such as SP-A, SP-B and SP-D. The results obtained are summarised as follows : 1） The levels of total protein and phospholipid in alv 2 and SA fractions increased in NMU-injected rats through day 7, indicating that pool sizes of small aggregate-formed surfactant （SA-SC, which almost completely represented the phospholipid content, had increased in the alveolar space in the acute lung injury. This result suggests that a conversion of large aggregate-formed surfactant （LA-Sf） to SA-Sf might be induced in the alveoli by the acute lung injury. 2） In NMU-injected rats, SP-A, SP-B and SP-D levels in BAL-subfractions were altered differently. SP-A and SP--B levels in LA fraction of NMU-injected rats were markedly lower than normal on day 2 （88.3 μg/rat on day 0 to 14.9 μg/rat on day 2 for SP-A, and 12.6 μg/rat to 1.5 μg/rat for SP-B, respectively）. Then, the SP-A levels in alv 1 and LA fractions returned gradually to about 50-60% of the first levels through day 7, while the SP-B levels in both fractions remained at almost the same diminished levels. SP-D levels in alv 2 and SA fractions of NMU-injected rats were markedly higher than controls on day 4. SP-A and SP-B levels in SA fraction and SP-D levels in LA fraction of NMU-injected rats were not altered significantly during the experimental periods. 3） The ?H-LA faction was isolated from culture media of rat alveolar type II cells labeled with ?H- choline for 20 hrs, followed by treatment with TPA and incubation for 18 hrs with BAL fluid obtained NMU-injected rats. About 95% of the ?H-LA converted to SA fration, indicating that a factor capable of converting LA-Sf to SA-Sf may be contained in the BAL.departmental bulletin pape