title: ICAM-1 induction in respiratory cells exposed to a replication-deficient recombinant adenovirus in vitro and in vivo.
abstract: 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 possibly involved, we investigated the expression of intercellular adhesion molecule-1 (ICAM-1), which is known to be induced by parainfluenza, adenovirus type 5 and respiratory syncytial viruses in vitro. To test this 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 epithelial cell line) or instilled by bronchoscopic procedures into the airways of Rhesus monkeys. Ad.CFTR induced expression of ICAM-1 in A549 cells and up-regulated with time the basal levels of ICAM-1 mRNA in lung portions of Rhesus monkeys. These observations indicate that E1-E3-deleted replication-deficient adenoviral vectors are capable of inducing adhesion molecules known to play a role in inflammation.
authors.affiliation: Cystic Fibrosis Center, Azienda Ospedaliera Verona, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Nicolis
authors.forename: A
authors.initials: A
authors.lastname: Tamanini
authors.forename: P
authors.initials: P
authors.lastname: Melotti
authors.forename: R
authors.initials: R
authors.lastname: Rolfini
authors.forename: G
authors.initials: G
authors.lastname: Berton
authors.forename: M A
authors.initials: MA
authors.lastname: Cassatella
authors.forename: A
authors.initials: A
authors.lastname: Bout
authors.forename: A
authors.initials: A
authors.lastname: Pavirani
authors.forename: G
authors.initials: G
authors.lastname: Cabrini
mesh_terms: D000256:Adenoviridae; D000818:Animals; D002460:Cell Line; D003550:Cystic Fibrosis / Q000378:metabolism / Q000628:therapy*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005786:Gene Expression Regulation; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D008168:Lung / Q000378:metabolism; D008253:Macaca mulatta; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: C505032:CFTR protein, human; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D019005:Cystic Fibrosis Transmembrane Conductance Regulator