Bleomycin stimulates lung fibroblast and epithelial cell lines to release eosinophil chemotactic activity

The presence of eosinophils in the lungs of patients with pulmonary fibrosi s correlates with poor prognosis or resistance to therapy. Furthermore, eos inophils localize to areas undergoing active fibrosis. It was hypothesized that a human lung fibroblast (HFL-1) and a human lung epithelial cell line (BEAS-2B) might release eosinophil chemotactic activity (ECA) in response t o bleomycin, a chemotherapeutic agent associated with pulmonary fibrosis. HFL-1 and BEAS-2B cells were cultured in the presence of bleomycin and thei r supernatant fluids evaluated for ECA by means of a Boyden chamber method. HFL-1 and BEAS-2B cells released ECA in a dose- and time-dependent manner i n response to bleomycin, and partial characterization revealed that the ECA was heterogeneous. ECA release from HFL-1 and BEAS-2B cells was significan tly reduced by a leukotriene B-4 (LTB4) receptor antagonist and an antibody directed against granulocyte-macrophage colony-stimulating factor. HFL-1 c ells released LTB4, eotaxin, and GM-CSF constitutively, and BEAS-2B cells r eleased LTB4, eotaxin, regulated on activation, normal T-cell expressed and presumably secreted, and GM-CSF constitutively. In both cases, the release of GM-CSF was significantly increased in response to bleomycin. These data suggest that lung fibroblasts and epithelial cells may modulate eosinophil recruitment into the lung in bleomycin-induced pulmonary fibrosi s.