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 transgene expression in the liver. This technique was tested in salivary glands. Rats were treated with Cl2MBP-liposomes or control liposomes by femoral vein, intraperitoneal, 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 macrophages 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 adenoviral-mediated transgene expression, this strategy was ineffective for salivary glands.
Wang
S
S
Gene Therapy and Therapeutics Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892-1190, USA.
Baum
B J
BJ
Kagami
H
H
Zheng
C
C
O'Connell
B C
BC
Atkinson
J C
JC
D000256:Adenoviridae; D000818:Animals; D004002:Clodronic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D007267:Injections; D007728:Kupffer Cells / Q000201:enzymology / Q000276:immunology; D008081:Liposomes / Q000008:administration & dosage; D008156:Luciferases / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D009928:Organ Specificity; D010306:Parotid Gland / Q000201:enzymology / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D013363:Submandibular Gland / Q000201:enzymology / Q000276:immunology*
D008081:Liposomes; D004002:Clodronic Acid; D008156:Luciferases