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Effect of clodronate on macrophage depletion and adenoviral‐mediated transgene expression in salivary glands
Author(s) -
Wang Songlin,
Baum Bruce J.,
Kagami Hideaki,
Zheng Changyu,
O'Connell Brain C,
Atkinson Jane C.
Publication year - 1999
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/j.1600-0714.1999.tb02014.x
Subject(s) - transgene , liposome , salivary gland , luciferase , genetically modified mouse , adenoviridae , macrophage , biology , medicine , chemistry , microbiology and biotechnology , endocrinology , recombinant dna , in vitro , transfection , cell culture , biochemistry , genetics , gene
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 (Cl 2 MBP) increases adenoviral‐mediated transgene expression in the liver. This technique was tested in salivary glands. Rats were treated with Cl 2 MBP‐liposomes or control liposomes by femoral vein, intraperitoneal, or carotid artery injections. Thereafter, a recombinant adenovirus, AdCMV luciferase, was instilled intraductally in submandibular glands (SMGs), or delivered to the liver via femoral vein injection. Marked depletion (>94%) of liver macrophages and increased levels of luciferase activity in the liver (45‐fold higher than controls) were present in animals receiving Cl 2 MBP‐liposomes. In contrast, the same treatment never depleted more than 41% of SMG macrphages nor increased luciferase activity in SMGs, regardless of the route of administration. In conclusion, while macrophage depletion with Cl 2 MBP‐liposomes is associated with markedly increased adenoviral‐mediated transgene expression, this strategy was ineffective for salivary glands.