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Blood, 15 January 2005, Vol. 105, No. 2, pp. 650-658. Prepublished online as a Blood First Edition Paper on September 14, 2004; DOI 10.1182/blood-2004-05-1714. This Article Full Text (PDF) All Versions of this Article: 2004-05-1714v1 105/2/650    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Muro, S. Articles by Muzykantov, V. R Search for Related Content PubMed PubMed Citation Articles by Muro, S. Articles by Muzykantov, V. R Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 4, 2004 Accepted August 30, 2004 ICAM-1 recycling in endothelial cells: a novel pathway for sustained intracellular delivery and prolonged effects of drugs Silvia Muro*, Christine Gajewski, Michael Koval, and Vladimir R Muzykantov Institute for Environmental Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA Institute for Environmental Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA Institute for Environmental Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA * Corresponding author; email: silvia{at}mail.med.upenn.edu. ICAM-1 is a target for drug delivery to endothelial cells (EC), which internalize multivalent anti-ICAM nanocarriers (anti-ICAM/NC) within 15-30 min. The concomitant ICAM-1 disappearance from the EC surface transiently inhibited subsequent binding and uptake of anti-ICAM/NC. Within 1 h, internalized ICAM-1 diverged from anti-ICAM/NC into pre-lysosomal vesicles, resurfaced and enabled uptake of a subsequent anti-ICAM/NC dose. Thus, internalized ICAM-1 was able to recycle back to the plasma membrane. In vivo pulmonary targeting of a second anti-ICAM/NC dose injected 15 min after the first dose was decreased by 50%, but recovered between 30 min and 2.5 h, comparable to cultured EC. Anti-ICAM/NC affected neither EC viability nor fluid-phase endocytosis and traffic to lysosomes. However, lysosomal trafficking of the second dose of anti-ICAM/NC was decelerated at least two-fold vs. the first dose; hence the major fraction of anti-ICAM/NC resided in pre-lysosomal vesicles for at least 5 h without degradation. Two successive doses of anti-ICAM/NC/catalase protected EC against H2O2 for at least 8 h vs 2 h afforded by a single dose, suggesting that recurrent targeting to ICAM-1 affords longer effects. ICAM-1 recycling and inhibited lysosomal traffic/degradation of subsequent doses may help to prolong activity of therapeutic agents delivered into EC by anti-ICAM/NC. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Garnacho, V. Shuvaev, A. Thomas, L. McKenna, J. Sun, M. Koval, S. Albelda, V. Muzykantov, and S. Muro RhoA activation and actin reorganization involved in endothelial CAM-mediated endocytosis of anti-PECAM carriers: critical role for tyrosine 686 in the cytoplasmic tail of PECAM-1 Blood, March 15, 2008; 111(6): 3024 - 3033. [Abstract] [Full Text] [PDF] R. Rossin, S. Muro, M. J. Welch, V. R. Muzykantov, and D. P. Schuster In Vivo Imaging of 64Cu-Labeled Polymer Nanoparticles Targeted to the Lung Endothelium J. Nucl. Med., January 1, 2008; 49(1): 103 - 111. [Abstract] [Full Text] [PDF] S. Patschan, J. Chen, O. Gealekman, K. Krupincza, M. Wang, L. Shu, J. A. Shayman, and M. S. Goligorsky Mapping mechanisms and charting the time course of premature cell senescence and apoptosis: lysosomal dysfunction and ganglioside accumulation in endothelial cells Am J Physiol Renal Physiol, January 1, 2008; 294(1): F100 - F109. [Abstract] [Full Text] [PDF] S. Muro, T. Dziubla, W. Qiu, J. Leferovich, X. Cui, E. Berk, and V. R. Muzykantov Endothelial Targeting of High-Affinity Multivalent Polymer Nanocarriers Directed to Intercellular Adhesion Molecule 1 J. Pharmacol. Exp. Ther., June 1, 2006; 317(3): 1161 - 1169. [Abstract] [Full Text] [PDF] R. V. Stan Endocytosis pathways in endothelium: how many? Am J Physiol Lung Cell Mol Physiol, May 1, 2006; 290(5): L806 - L808. [Full Text] [PDF] S. Muro, M. Mateescu, C. Gajewski, M. Robinson, V. R. Muzykantov, and M. Koval Control of intracellular trafficking of ICAM-1-targeted nanocarriers by endothelial Na+/H+ exchanger proteins Am J Physiol Lung Cell Mol Physiol, May 1, 2006; 290(5): L809 - L817. [Abstract] [Full Text] [PDF] B.-S. Ding, T. Dziubla, V. V. Shuvaev, S. Muro, and V. R. Muzykantov Advanced drug delivery systems that target the vascular endothelium. Mol. Interv., April 1, 2006; 6(2): 98 - 112. [Abstract] [Full Text] [PDF]

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