Interferon-gamma stimulates fractalkine expression in human bronchial epithelial cells and regulates mononuclear cell adherence

Bronchial epithelial cells may contribute to airway inflammation by releasi ng chemokines and expressing surface membrane molecules involved in the adh esion of leukocytes. We found that interferon (IFN)-gamma stimulates expres sion of fractalkine, a potent chemoattractant for monocytes and T lymphocyt es, in a time- and concentration-dependent manner by normal human bronchial epithelial cells in culture. Enhanced expression of fractalkine messenger RNA was confirmed by both reverse transcription/polymerase chain reaction a nd Northern blotting. IFN-gamma also stimulated fractalkine protein product ion and most of the protein was found in cell lysates. The adherence of blo od mononuclear cells to the monolayers of bronchial epithelial cells stimul ated with IFN-gamma was partly inhibited by an antifractalkine antibody. An antibody against intercellular adhesion molecule-1 was similarly effective in inhibiting the adhesion. Fractalkine protein levels in bronchoalveolar lavage fluids from patients with inflammatory diseases correlated positivel y with mononuclear cell counts in the fluids. The bronchial epithelium in a biopsy specimen of lung cancer was stained positively by immunofluorescent staining for fractalkine. We conclude that IFN-gamma stimulates fractalkin e expression by bronchial epithelial cells, which may play an important rol e in inflammatory responses by recruiting mononuclear leukocytes to the bro nchial epithelium.