ICAM-1 INDUCTION IN RESPIRATORY CELLS EXPOSED TO A REPLICATION-DEFICIENT RECOMBINANT ADENOVIRUS IN-VITRO AND IN-VIVO

Administration of replication-deficient recombinant adenoviruses (Ad) designed as vectors for gene transfer to the airway tract of rats and monkeys has been associated with a dose-dependent inflammatory process a few days after viral exposure. Among the cellular mechanisms possib ly involved, we investigated the expression of intercellular adhesion molecule-1 (ICAM-1), which is known to be induced by parainfluenza, ad enovirus type 5 and respiratory syncytial viruses in vitro. To test th is hypothesis, an Ad type 5-derived replication-deficient recombinant vector carrying the expression cassette for the cystic fibrosis gene ( Ad.CFTR) was either incubated with A549 cells (a human-derived lung ep ithelial cell line) or instilled by bronchoscopic procedures into the airways of Rhesus monkeys. Ad.CFTR induced expression of ICAM-1 in A54 9 cells and up-regulated with time the basal levels of ICAM-1 mRNA in lung portions of Rhesus monkeys. These observations indicate that E1-E 3-deleted replication-deficient adenoviral vectors are capable of indu cing adhesion molecules known to play a role in inflammation.