Cytotoxic Factor for Fibroblasts in Bronchoalveolar Lavage Fluid of Bleomycin-Treated Rats

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Abstract
The mechanism of lung injury and fibrosis in diffuse interstitial lung disease were studied by tests on the in vitro effect of bronchoalveolar lavage fluid (BALF) from bleomycin-treated rats on quiescent fibroblasts in culture. The BALF was obtained on days 2, 3, 6, 15, and 29 after intratracheal administration of bleomycin. Cytotoxic activity was detected in the BALF only on day 2. The factor responsible for the cytotoxic activity was detected in 50-70% ammonium sulfate fraction, and lost 10% of its activity after 30 min at 56.degree.C, 75% after 10 min at 80.degree.C, and all activity after 10 min at 100.degree.C. The factor was completely precipitated by 60% acetone and was not extractable with ether. In ion exchange chromatography, the factor was eluted with the main fraction of protein, and gel filtration indicated that it had a molecular weight of 60-70 kDa. Histological examination showed disappearance of the normal alveolar architecture on day 2, and pulmonary fibrosis on day 15. Thus the cytotoxic factor may be one of factors responsible for lung injury and may act as trigger for subsequent fibrosis in bleomycin-induced lung damage.