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Am. J. Respir. Cell Mol. Biol., Volume 25, Number 2, August, 2001 233-238

Interferon-gamma Stimulates Fractalkine Expression in Human Bronchial Epithelial Cells and Regulates Mononuclear Cell Adherence

Koji Fujimoto, Tadaatsu Imaizumi, Hidemi Yoshida, Shingo Takanashi, Ken Okumura, and Kei Satoh

Department of Vascular Biology, Institute of Brain Science; and The Second Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki, Japan

Bronchial epithelial cells may contribute to airway inflammation by releasing chemokines and expressing surface membrane molecules involved in the adhesion of leukocytes. We found that interferon (IFN)-gamma stimulates expression of fractalkine, a potent chemoattractant for monocytes and T lymphocytes, 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 and Northern blotting. IFN-gamma also stimulated fractalkine protein production and most of the protein was found in cell lysates. The adherence of blood mononuclear cells to the monolayers of bronchial epithelial cells stimulated 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 positively 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 fractalkine expression by bronchial epithelial cells, which may play an important role in inflammatory responses by recruiting mononuclear leukocytes to the bronchial epithelium.

Abbreviations: bronchoalveolar lavage fluid, BALF; digoxygenin, DIG; enzyme-linked immunosorbent assay, ELISA; glyceraldehyde-3-phosphate dehydrogenase, GAPDH, intercellular adhesion molecule, ICAM; interferon, IFN; immunoglobulin, Ig; monocyte chemotactic protein, MCP; messenger RNA, mRNA; polymerase chain reaction, PCR; polymorphonuclear neutrophil, PMN; reverse transcriptase, RT.




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