Methotrexate stimulates lung fibroblasts and epithelial cells to release eosinophil chemotactic activity

Objective. To determine if methotrexate (MTX) induces human lung fibroblast (HFL-1) and epithelial (BEAS 2B) cell lines to release eosinophil chemotac tic activity (ECA). Methods. HFL-1 and BEAS 2B cell supernatant fluids were evaluated for ECA b y a blind well chamber technique. Results. HFL-1 and BEAS-2B cells released ECA in a dose and time dependent manner in response to MTX. Partial characterization revealed that ECA was p artly heat labile, trypsin sensitive, and ethylacetate extractable. Thus th e culture supernatant fluids were evaluated for known eosinophil chemotacti c factors, Although several were released constitutively, granulocyte-macro phage colony-stimulating factor (GM-CSF) was significantly increased in res ponse to MTX from both cell types. Consistent with these observations, ECA from both cell types was inhibited by GM-CSF antibodies. Conclusion. These data suggest that lung fibroblasts and epithelial cells m ay modulate eosinophil recruitment into the lung by releasing ECA in respon se to MTX.