AJP - Lung Watch the video to learn how APS reaches out to developing nations.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Lung Cell Mol Physiol 278: L504-L511, 2000;
1040-0605/00 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (45)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Li, S.
Right arrow Articles by Huang, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Li, S.
Right arrow Articles by Huang, L.
Vol. 278, Issue 3, L504-L511, March 2000

Targeted gene delivery to pulmonary endothelium by anti-PECAM antibody

Song Li, Yadi Tan, Ekapop Viroonchatapan, Bruce R. Pitt, and Leaf Huang

Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261

To achieve efficient systemic gene delivery to the lung with minimal toxicity, a vector was developed by chemically conjugating a cationic polymer, polyethylenimine (PEI), with anti-platelet endothelial cell adhesion molecule (PECAM) antibody (Ab). Transfection of mouse lung endothelial cells with a plasmid expression vector with cDNA to luciferase (pCMVL) complexed with anti-PECAM Ab-PEI conjugate was more efficient than that with PEI-pCMVL complexes. Furthermore, the anti-PECAM Ab-PEI conjugate mediated efficient transfection at lower charge plus-to-minus ratios. Conjugation of PEI with a control IgG (hamster IgG) did not enhance transfection of mouse lung endothelial cells, suggesting that the cellular uptake of anti-PECAM Ab-PEI-DNA complexes and subsequent gene expression were governed by a receptor-mediated process rather than by a nonspecific charge interaction. Conjugation of PEI with anti-PECAM Ab also led to significant improvement in lung gene transfer to intact mice after intravenous administration. The increase in lung transfection was associated with a decrease compared with PEI-pCMVL with respect to circulating proinflammatory cytokine (tumor necrosis factor-alpha ) levels. These results indicate that targeted gene delivery to the lung endothelium is an effective strategy to enhance gene delivery to the pulmonary circulation while simultaneously reducing toxicity.

cationic polymer; plasmid deoxyribonucleic acid; gene transfer; targeting; toxicity


This article has been cited by other articles:


Home page
 J. Pharmacol. Exp. Ther.Home page
V. V. Shuvaev, M. Christofidou-Solomidou, F. Bhora, K. Laude, H. Cai, S. Dikalov, E. Arguiri, C. C. Solomides, S. M. Albelda, D. G. Harrison, et al.
Targeted Detoxification of Selected Reactive Oxygen Species in the Vascular Endothelium
J. Pharmacol. Exp. Ther., November 1, 2009; 331(2): 404 - 411.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
M. Christofidou-Solomidou, A. Scherpereel, R. Wiewrodt, K. Ng, T. Sweitzer, E. Arguiri, V. Shuvaev, C. C. Solomides, S. M. Albelda, and V. R. Muzykantov
PECAM-directed delivery of catalase to endothelium protects against pulmonary vascular oxidative stress
Am J Physiol Lung Cell Mol Physiol, August 1, 2003; 285(2): L283 - L292.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
S. Muro, R. Wiewrodt, A. Thomas, L. Koniaris, S. M. Albelda, V. R. Muzykantov, and M. Koval
A novel endocytic pathway induced by clustering endothelial ICAM-1 or PECAM-1
J. Cell Sci., April 15, 2003; 116(8): 1599 - 1609.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
Z. Ma, J. Zhang, S. Alber, J. Dileo, Y. Negishi, D. Stolz, S. Watkins, L. Huang, B. Pitt, and S. Li
Lipid-Mediated Delivery of Oligonucleotide to Pulmonary Endothelium
Am. J. Respir. Cell Mol. Biol., August 1, 2002; 27(2): 151 - 159.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
A. Scherpereel, J. J. Rome, R. Wiewrodt, S. C. Watkins, D. W. Harshaw, S. Alder, M. Christofidou-Solomidou, E. Haut, J.-C. Murciano, M. Nakada, et al.
Platelet-Endothelial Cell Adhesion Molecule-1-Directed Immunotargeting to Cardiopulmonary Vasculature
J. Pharmacol. Exp. Ther., March 1, 2002; 300(3): 777 - 786.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
R. Wiewrodt, A. P. Thomas, L. Cipelletti, M. Christofidou-Solomidou, D. A. Weitz, S. I. Feinstein, D. Schaffer, S. M. Albelda, M. Koval, and V. R. Muzykantov
Size-dependent intracellular immunotargeting of therapeutic cargoes into endothelial cells
Blood, February 1, 2002; 99(3): 912 - 922.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
J. C. MURCIANO, D. WIN HARSHAW, L. GHITESCU, S. M. DANILOV, and V. R. MUZYKANTOV
Vascular Immunotargeting to Endothelial Surface in a Specific Macrodomain in Alveolar Capillaries
Am. J. Respir. Crit. Care Med., October 1, 2001; 164(7): 1295 - 1302.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
S. M. Danilov, V. D. Gavrilyuk, F. E. Franke, K. Pauls, D. W. Harshaw, T. D. McDonald, D. J. Miletich, and V. R. Muzykantov
Lung uptake of antibodies to endothelial antigens: key determinants of vascular immunotargeting
Am J Physiol Lung Cell Mol Physiol, June 1, 2001; 280(6): L1335 - L1347.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online