EXPRESSION OF RANTES BY NORMAL AIRWAY EPITHELIAL-CELLS AFTER INFLUENZA-VIRUS-A INFECTION

The chemokine regulated on activation, normal T cells expressed and se creted (RANTES), is a C-C chemokine and a potent chemoattractant for m onocytes, T lymphocytes, basophils, and eosinophils. Its expression by human airway epithelium has been demonstrated both in vitro and in vi vo. We investigated whether RANTES is expressed by normal human airway epithelial cells after influenza viral infection and examined its bio activity. Epithelial cells were obtained from bronchial tissue or nasa l polyps of patients who had undergone lobectomy for lung cancer or po lypectomy for nasal polyps. These cells were cultured by the outgrowth method. Cultured cells were infected with influenza virus A (subtype H3N2) after which the supernatants and the cells were collected 8 to 7 2 h after infection. RANTES mRNA (messenger RNA) was analyzed by the r everse transcriptase-polymerase chain reaction and Southern blot analy sis of its product. Concentrations of RANTES in the supernatants were analyzed by enzyme-linked immunosorbent assay. RANTES protein and mRNA were not detected in the media of uninfected cells. PCR products for RANTES were clearly detected in nasal and bronchial epithelial cells 2 4 h after infection. Southern blot analysis confirmed that the PCR pro ducts were indeed specific for RANTES mRNA. Twenty-four to 72 h after infection, significant levels of RANTES protein were detected in cultu re media. We also investigated the chemotactic activity of the superna tant of cultured cells. The supernatant of the cells 48 h after infect ion had potent chemotactic activity for eosinophils, which was attenua ted by the addition of anti-RANTES antibodies. These findings suggest that influenza virus infection may induce expression of bioactive RANT ES by normal human bronchial and nasal epithelial cells.