In Vivo Collagen Accumulation in an Experimental Model of Pulmonary Fibrosis

Abstract

Pulmonary fibrosis developed within 2 weeks in mice treated initially with butylated hydroxytoluene (BHT) and immediately exposed to 70% oxygen for 6 days. The total lung hydroxy-proline content of these mice increased only moderately until the oxygen exposure ended. A rapid increase in total lung hydroxyproline followed, with maximum levels being achieved by day 15. The formation of acid-insoluble radiolabeled hydroxyproline following the in vivo administration of [³H]proline was measured during the development of fibrosis. Only a small increase in [³H] hydroxyproline accumulation was measured in BHT-treated mice during the six-day hyper-oxic exposure. Thereafter a rapid increase in the accumulation of [³H] hydroxyproline occurred, with maximum levels appearing 7 days after the administration of BHT. The percentage of total [³H] hydroxyproline formed from [³H]proline which was acid soluble, an indication of the degradation of newly synthesized collagen, was significantly decreased in mice treated with BHT and exposed to 70% oxygen. Calculating net hydroxyproline synthesis as a percentage of total lung protein synthesis devoted to collagen production demonstrated that there was a specific stimulation of collagen synthesis in this model of pulmonary fibrosis. Increases in [³H]hydroxyproline accumulation and decreases in the degradation of newly synthesized collagen observed in mice treated with BHT and left in room air were less extensive than those seen in mice treated with BHT and exposed to oxygen, and rapidly returned to control levels.