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  • Title: ICAM-1 induction in respiratory cells exposed to a replication-deficient recombinant adenovirus in vitro and in vivo.
    Author: Nicolis E, Tamanini A, Melotti P, Rolfini R, Berton G, Cassatella MA, Bout A, Pavirani A, Cabrini G.
    Journal: Gene Ther; 1998 Jan; 5(1):131-6. PubMed ID: 9536274.
    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.
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