Alterations in Alveolar Macrophages in Hamsters Developing Pulmonary Fibrosis

Abstract

Hamsters treated with intratracheally instilled bleomycin (0.16 U/100 g) followed by a 72-hr exposure to 70% oxygen develop a slowly progressive interstitial pneumonitis with fibrosis. Lung lavage was performed during fibrogenesis at 30, 60, and 120 days after treatment. The number of macrophages recovered was increased at all of these times. Macrophages were evaluated using flow cytometry and a monoclonal antibody specific for a surface antigen present on mature lung macrophages but deficient in younger cells. The mean density of antigenic sites per cell surface area was significantly lower than control values at the three times studied (-24.7, -20.0, and -20.9%). Thus, a significant fraction of macrophages present in this model of progressive pulmonary fibrosis are immature. The in vivo uptake of radioactive colloidal gold by the pulmonary macrophages was also determined. Thirty days after treatment, macrophage endocytosis of colloidal gold was reduced by 22% of control. The total number of harvested macrophages increased twofold, however, a change that usually increases endocytotic rates. It is concluded that macrophages are increased during fibrogenesis and that this increase is caused by a continued influx of new macrophages. In addition, the phagocytic function of these macrophages is less efficient.