Article abstract
Nature Biotechnology 25, 327 - 337 (2007)
Published online: 4 March 2007 | doi:10.1038/nbt1292
There is an Erratum (April 2007) associated with this Article.
Live dynamic imaging of caveolae pumping targeted antibody rapidly and specifically across endothelium in the lung
Phil Oh1, Per Borgström1, Halina Witkiewicz1, Yan Li1, Bengt J Borgström2, Adrian Chrastina1, Koji Iwata3, Kurt R Zinn4, Richard Baldwin1, Jacqueline E Testa1 & Jan E Schnitzer1
Abstract
How effectively and quickly endothelial caveolae can transcytose in vivo is unknown, yet critical for understanding their function and potential clinical utility. Here we use quantitative proteomics to identify aminopeptidase P (APP) concentrated in caveolae of lung endothelium. Electron microscopy confirms this and shows that APP antibody targets nanoparticles to caveolae. Dynamic intravital fluorescence microscopy reveals that targeted caveolae operate effectively as pumps, moving antibody within seconds from blood across endothelium into lung tissue, even against a concentration gradient. This active transcytosis requires normal caveolin-1 expression. Whole body 
-scintigraphic imaging shows rapid, specific delivery into lung well beyond that achieved by standard vascular targeting. This caveolar trafficking in vivo may underscore a key physiological mechanism for selective transvascular exchange and may provide an enhanced delivery system for imaging agents, drugs, gene-therapy vectors and nanomedicines. 'In vivo proteomic imaging' as described here integrates organellar proteomics with multiple imaging techniques to identify an accessible target space that includes the transvascular pumping space of the caveola.
- Sidney Kimmel Cancer Center, 10905 Road to the Cure, San Diego, California 92121, USA.
- EE Department, University of California, Los Angeles, Box 951594, Los Angeles, California 90095, USA.
- Gamma Medica, Inc., 19355 Business Center Drive, Suite #18, Northridge, California 91324, USA.
- Departments of Medicine, Radiology & Pathology, University of Alabama at Birmingham, 1808 Seventh Avenue South, Birmingham, Alabama 35294, USA.
Correspondence to: Jan E Schnitzer1 e-mail: jschnitzer@skcc.org
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