|
|
|
|
|
|
|
|
|||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
doi: 10.1242/10.1242/jcs.00367
Research Article |
1 Department of Physiology, University of Pennsylvania School of Medicine, B-400
Richards/6085, 3700 Hamilton Walk, Philadelphia, PA 19104, USA
2 Department of Pharmacology and Medicine, Pulmonary, University of Pennsylvania
School of Medicine, B-400 Richards/6085, 3700 Hamilton Walk, Philadelphia, PA
19104, USA
3 Department of Critical Care Division, University of Pennsylvania School of
Medicine, B-400 Richards/6085, 3700 Hamilton Walk, Philadelphia, PA 19104,
USA
4 Institute for Environmental Medicine, University of Pennsylvania School of
Medicine, B-400 Richards/6085, 3700 Hamilton Walk, Philadelphia, PA 19104,
USA
* Authors for correspondence (e-mail: mkoval{at}mail.med.upenn.edu, muzykant{at}mail.med.upenn.edu)
Accepted 14 February 2003
Antibody conjugates directed against intercellular adhesion molecule (ICAM-1) or platelet-endothelial cell adhesion molecule (PECAM-1) have formed the basis for drug delivery vehicles that are specifically recognized and internalized by endothelial cells. There is increasing evidence that ICAM-1 and PECAM-1 may also play a role in cell scavenger functions and pathogen entry. To define the mechanisms that regulate ICAM-1 and PECAM-1 internalization, we examined the uptake of anti-PECAM-1 and anti-ICAM-1 conjugates by endothelial cells. We found that the conjugates must be multimeric, because monomeric anti-ICAM-1 and anti-PECAM-1 are not internalized. Newly internalized anti-ICAM-1 and anti-PECAM-1 conjugates did not colocalize with either clathrin or caveolin, and immunoconjugate internalization was not reduced by inhibitors of clathrin-mediated or caveolar endocytosis, suggesting that this is a novel endocytic pathway. Amiloride and protein kinase C (PKC) inhibitors, agents known to inhibit macropinocytosis, reduced the internalization of clustered ICAM-1 and PECAM-1. However, expression of dominant-negative dynamin-2 constructs inhibited uptake of clustered ICAM-1. Binding of anti-ICAM-1 conjugates stimulated the formation of actin stress fibers by human umbilical vein endothelial cells (HUVEC). Latrunculin, radicicol and Y27632 also inhibited internalization of clustered ICAM-1, suggesting that actin rearrangements requiring Src kinase and Rho kinase (ROCK) were required for internalization. Interestingly, these kinases are part of the signal transduction pathways that are activated when circulating leukocytes engage endothelial cell adhesion molecules, suggesting the possibility that CAM-mediated endocytosis is regulated using comparable signaling pathways.
Key words: HUVEC, Vascular endothelium, Cell adhesion, Macropinocytosis, Endocytosis
Related articles in JCS:
This article has been cited by other articles:
|
|
 |
|
  C. Garnacho, R. Dhami, E. Simone, T. Dziubla, J. Leferovich, E. H. Schuchman, V. Muzykantov, and S. Muro Delivery of Acid Sphingomyelinase in Normal and Niemann-Pick Disease Mice Using Intercellular Adhesion Molecule-1-Targeted Polymer Nanocarriers J. Pharmacol. Exp. Ther., May 1, 2008; 325(2): 400 - 408. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 S. H. Ramirez, D. Heilman, B. Morsey, R. Potula, J. Haorah, and Y. Persidsky Activation of Peroxisome Proliferator-Activated Receptor {gamma} (PPAR{gamma}) Suppresses Rho GTPases in Human Brain Microvascular Endothelial Cells and Inhibits Adhesion and Transendothelial Migration of HIV-1 Infected Monocytes J. Immunol., February 1, 2008; 180(3): 1854 - 1865. [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]
|
|
|
|
|
|
V. V. Shuvaev, S. Tliba, M. Nakada, S. M. Albelda, and V. R. Muzykantov Platelet-Endothelial Cell Adhesion Molecule-1-Directed Endothelial Targeting of Superoxide Dismutase Alleviates Oxidative Stress Caused by Either Extracellular or Intracellular Superoxide J. Pharmacol. Exp. Ther., November 1, 2007; 323(2): 450 - 457. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. N. Atapattu and C. J. Czuprynski Mannheimia haemolytica Leukotoxin Binds to Lipid Rafts in Bovine Lymphoblastoid Cells and Is Internalized in a Dynamin-2- and Clathrin-Dependent Manner Infect. Immun., October 1, 2007; 75(10): 4719 - 4727. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. van Buul, E. Kanters, and P. L. Hordijk Endothelial Signaling by Ig-Like Cell Adhesion Molecules Arterioscler. Thromb. Vasc. Biol., September 1, 2007; 27(9): 1870 - 1876. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Gilbert, R. Cantin, C. Barat, and M. J. Tremblay Human Immunodeficiency Virus Type 1 Replication in Dendritic Cell-T-Cell Cocultures Is Increased upon Incorporation of Host LFA-1 due to Higher Levels of Virus Production in Immature Dendritic Cells J. Virol., July 15, 2007; 81(14): 7672 - 7682. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. Dada, E. Novoa, E. Lecuona, H. Sun, and J. I. Sznajder Role of the small GTPase RhoA in the hypoxia-induced decrease of plasma membrane Na,K-ATPase in A549 cells J. Cell Sci., July 1, 2007; 120(13): 2214 - 2222. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Danielyan, B.-S. Ding, C. Gottstein, D. B. Cines, and V. R. Muzykantov Delivery of Anti-Platelet-Endothelial Cell Adhesion Molecule Single-Chain Variable Fragment-Urokinase Fusion Protein to the Cerebral Vasculature Lyses Arterial Clots and Attenuates Postischemic Brain Edema J. Pharmacol. Exp. Ther., June 1, 2007; 321(3): 947 - 952. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Falcone, E. Cocucci, P. Podini, T. Kirchhausen, E. Clementi, and J. Meldolesi Macropinocytosis: regulated coordination of endocytic and exocytic membrane traffic events J. Cell Sci., November 15, 2006; 119(22): 4758 - 4769. [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]
|
|
|
|
 |
|
 L. Tomasinsig, B. Skerlavaj, N. Papo, B. Giabbai, Y. Shai, and M. Zanetti Mechanistic and Functional Studies of the Interaction of a Proline-rich Antimicrobial Peptide with Mammalian Cells J. Biol. Chem., January 6, 2006; 281(1): 383 - 391. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.-S. Ding, C. Gottstein, A. Grunow, A. Kuo, K. Ganguly, S. M. Albelda, D. B. Cines, and V. R. Muzykantov Endothelial targeting of a recombinant construct fusing a PECAM-1 single-chain variable antibody fragment (scFv) with prourokinase facilitates prophylactic thrombolysis in the pulmonary vasculature Blood, December 15, 2005; 106(13): 4191 - 4198. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Tamai, Y. Asai, and T. Ogawa Requirement for Intercellular Adhesion Molecule 1 and Caveolae in Invasion of Human Oral Epithelial Cells by Porphyromonas gingivalis Infect. Immun., October 1, 2005; 73(10): 6290 - 6298. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Misinzo, P. Meerts, M. Bublot, J. Mast, H. M. Weingartl, and H. J. Nauwynck Binding and entry characteristics of porcine circovirus 2 in cells of the porcine monocytic line 3D4/31 J. Gen. Virol., July 1, 2005; 86(7): 2057 - 2068. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Muro, C. Gajewski, M. Koval, and V. R. Muzykantov ICAM-1 recycling in endothelial cells: a novel pathway for sustained intracellular delivery and prolonged effects of drugs Blood, January 15, 2005; 105(2): 650 - 658. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Soghomonians, T. L. Thirkill, N. F. Mariano, A. I. Barakat, and G. C. Douglas Effect of Aqueous Tobacco Smoke Extract and Shear Stress on PECAM-1 Expression and Cell Motility in Human Uterine Endothelial Cells Toxicol. Sci., October 1, 2004; 81(2): 408 - 418. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. K. Harvey, S. C. Anderson, and N. SundarRaj Downstream Effects of ROCK Signaling in Cultured Human Corneal Stromal Cells: Microarray Analysis of Gene Expression Invest. Ophthalmol. Vis. Sci., July 1, 2004; 45(7): 2168 - 2176. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Tkachenko, E. Lutgens, R.-V. Stan, and M. Simons Fibroblast growth factor 2 endocytosis in endothelial cells proceed via syndecan-4-dependent activation of Rac1 and a Cdc42-dependent macropinocytic pathway J. Cell Sci., July 1, 2004; 117(15): 3189 - 3199. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Imelli, O. Meier, K. Boucke, S. Hemmi, and U. F. Greber Cholesterol Is Required for Endocytosis and Endosomal Escape of Adenovirus Type 2 J. Virol., March 15, 2004; 78(6): 3089 - 3098. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Muro, X. Cui, C. Gajewski, J.-C. Murciano, V. R. Muzykantov, and M. Koval Slow intracellular trafficking of catalase nanoparticles targeted to ICAM-1 protects endothelial cells from oxidative stress Am J Physiol Cell Physiol, November 1, 2003; 285(5): C1339 - C1347. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
