Respiratory distress after intratracheal bleomycin: selective deficiency of surfactant proteins B and C

Intratracheal bleomycin in rats is associated with respiratory distress of uncertain etiology. We investigated the expression of surfactant components in this model of lung injury. Maximum respiratory distress, determined by respiratory rate, occurred at 7 days, and surfactant dysfunction was confir med by increased surface tension of the large-aggregate fraction of broncho alveolar lavage (BAL). In injured animals, phospholipid content and composi tion were similar to those of controls, mature surfactant protein (SP) B wa s decreased 90%, and SP-A and SP-D contents were increased. In lung tissue, SP-B and SP-C mRNAs were decreased by 2 days and maximally at 4-7 days and recovered between 14 and 21 days after injury. Immunostaining of SP-B and proSP-C was decreased in type Il epithelial cells but strong in macrophages . By electron microscopy, injured lungs had type II cells lacking lamellar bodies and macrophages with phagocytosed lamellar bodies. Surface activity of BAL phospholipids of injured animals was restored by addition of exogeno us SP-B. We conclude that respiratory distress after bleomycin in rats resu lts from surfactant dysfunction in part secondary to selective downregulati on. of SP-B and SP-C.