Effect of clodronate on macrophage depletion and adenoviral-mediated transgene expression in salivary glands.

Expression of transgenes from adenoviral vectors is short-lived in salivary glands, in part because of immune responses to the virus and/or transgene product. Previous studies demonstrated that depletion of macrophages with multilamellar liposomes containing clodronate (Cl₂MBP) increases adenoviral-mediated trans- gene expression in the liver. This technique was tested in salivary glands. Rats were treated with Cl₂MBP-liposomes or control liposomes by femoral vein, intra- peritoneal, or carotid artery injections. Thereafter, a recombinant adenovirus, AdCMVluciferase, was instilled intraductally in submandibular glands (SMGs), or delivered to the liver via femoral vein injection. Marked depletion (>94%) of liver maorophages and increased levels of luciferase activity in the Liver (45-fold higher than controls) were present in animals receiving Cl₂MBP-liposomes. In contrast, the same treatment never depleted more than 41% of SMG macrophages nor increased luciferase activity in SMGs, regardless of the route of administration. In conclusion, while macrophage depletion with Cl₂MBP-liposomes is associated with markedly increased adanoviral-mediated transgene expression, this strategy was ineffective for salivary glands. [ABSTRACT FROM AUTHOR]