Importance of E-Selectin for Firm Leukocyte Adhesion In Vivo

From the Department of Biomedical Engineering, University of Virginia School of Medicine, Charlottesville (K.L., M.A., S.M.), and Department of Comparative Medicine, University of Alabama at Birmingham (D.C.B.).

Correspondence to Klaus Ley, MD, University of Virginia Medical School, Department of Biomedical Engineering, Health Sciences Center, Box 377, Charlottesville, VA 22908. E-mail kfl3f{at}virginia.edu

Abstract—Leukocyte adhesion under flow is preferentially mediated by the selectins. In this study we used intravital microscopy to investigate whether E-selectin may promote firm leukocyte adhesion in vivo. E-Selectin is expressed by endothelial cells activated with tumor necrosis factor- (TNF-) and causes slow leukocyte rolling. Microinjection of formyl-methionyl-leucyl-phenylalanine (fMLP) or macrophage inflammatory protein-2 (MIP-2) next to a venule of the TNF-–treated mouse cremaster muscle significantly increased the number of adherent leukocytes. In gene-targeted mice homozygous for a null mutation in the E-selectin gene or in wild-type mice treated with an E-selectin monoclonal antibody (mAb), this response was significantly attenuated (by >80%). No such defect was seen in intercellular adhesion molecule-1 (ICAM-1)–deficient mice. E-Selectin–null mice showed more rapid leukocyte rolling than wild-type or ICAM-1–deficient mice, resulting in significantly shortened leukocyte transit times through venules. Topical application of fMLP onto the whole cremaster muscle generated the same number of adherent leukocytes in wild-type and E-selectin–deficient mice. We conclude that slow leukocyte rolling through E-selectin results in long transit times, which are essential for efficient leukocyte adhesion in response to a local chemotactic stimulus.

Key Words: E-selectin • rolling • leukocyte transit • ICAM-1 • leukocyte adhesion

This article has been cited by other articles:

				N. Kato, Y. Yuzawa, T. Kosugi, A. Hobo, W. Sato, Y. Miwa, K. Sakamoto, S. Matsuo, and K. Kadomatsu The E-Selectin Ligand Basigin/CD147 Is Responsible for Neutrophil Recruitment in Renal Ischemia/Reperfusion J. Am. Soc. Nephrol., July 1, 2009; 20(7): 1565 - 1576. [Abstract] [Full Text] [PDF]

				R. Sumagin and I. H. Sarelius A role for ICAM-1 in maintenance of leukocyte-endothelial cell rolling interactions in inflamed arterioles Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2786 - H2798. [Abstract] [Full Text] [PDF]

				A. L. Patrick, J. Rullo, S. Beaudin, P. Liaw, and A. E. Fox-Robichaud Hepatic leukocyte recruitment in response to time-limited expression of TNF-{alpha} and IL-1beta Am J Physiol Gastrointest Liver Physiol, October 1, 2007; 293(4): G663 - G672. [Abstract] [Full Text] [PDF]

				S. Thomas-Ecker, A. Lindecke, W. Hatzmann, C. Kaltschmidt, K. S. Zanker, and T. Dittmar Alteration in the gene expression pattern of primary monocytes after adhesion to endothelial cells PNAS, March 27, 2007; 104(13): 5539 - 5544. [Abstract] [Full Text] [PDF]

				U. M. Chandrasekharan, M. Siemionow, M. Unsal, L. Yang, E. Poptic, J. Bohn, K. Ozer, Z. Zhou, P. H. Howe, M. Penn, et al. Tumor necrosis factor {alpha} (TNF-{alpha}) receptor-II is required for TNF-{alpha}-induced leukocyte-endothelial interaction in vivo Blood, March 1, 2007; 109(5): 1938 - 1944. [Abstract] [Full Text] [PDF]

				R. Furst, T. Schroeder, H. M. Eilken, M. F. Bubik, A. K. Kiemer, S. Zahler, and A. M. Vollmar MAPK phosphatase-1 represents a novel anti-inflammatory target of glucocorticoids in the human endothelium FASEB J, January 1, 2007; 21(1): 74 - 80. [Abstract] [Full Text] [PDF]

				R. Sumagin and I. H. Sarelius TNF-{alpha} activation of arterioles and venules alters distribution and levels of ICAM-1 and affects leukocyte-endothelial cell interactions Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2116 - H2125. [Abstract] [Full Text] [PDF]

				S. C. Schafer, D. N. Sehrt, M. Kamler, H. Jakob, and H.-A. Lehr Paradoxical attenuation of leukocyte rolling in response to ischemia- reperfusion and extracorporeal blood circulation in inflamed tissue Am J Physiol Heart Circ Physiol, July 1, 2005; 289(1): H330 - H335. [Abstract] [Full Text] [PDF]

				L. Piccio, B. Rossi, L. Colantonio, R. Grenningloh, A. Gho, L. Ottoboni, J. W. Homeister, E. Scarpini, M. Martinello, C. Laudanna, et al. Efficient Recruitment of Lymphocytes in Inflamed Brain Venules Requires Expression of Cutaneous Lymphocyte Antigen and Fucosyltransferase-VII J. Immunol., May 1, 2005; 174(9): 5805 - 5813. [Abstract] [Full Text] [PDF]

				J. R. Mora, G. Cheng, D. Picarella, M. Briskin, N. Buchanan, and U. H. von Andrian Reciprocal and dynamic control of CD8 T cell homing by dendritic cells from skin- and gut-associated lymphoid tissues J. Exp. Med., January 18, 2005; 201(2): 303 - 316. [Abstract] [Full Text] [PDF]

				A. E. R. Hicks, K. B. Abbitt, P. Dodd, V. C. Ridger, P. G. Hellewell, and K. E. Norman The anti-inflammatory effects of a selectin ligand mimetic, TBC-1269, are not a result of competitive inhibition of leukocyte rolling in vivo J. Leukoc. Biol., January 1, 2005; 77(1): 59 - 66. [Abstract] [Full Text] [PDF]

				S. Cuzzocrea, G. Nocentini, R. Di Paola, E. Mazzon, S. Ronchetti, T. Genovese, C. Muia, A. P. Caputi, and C. Riccardi Glucocorticoid-induced TNF receptor family gene (GITR) knockout mice exhibit a resistance to splanchnic artery occlusion (SAO) shock J. Leukoc. Biol., November 1, 2004; 76(5): 933 - 940. [Abstract] [Full Text] [PDF]

				C. E. Green, D. N. Pearson, R. T. Camphausen, D. E. Staunton, and S. I. Simon Shear-Dependent Capping of L-Selectin and P-Selectin Glycoprotein Ligand 1 by E-Selectin Signals Activation of High-Avidity {beta}2-Integrin on Neutrophils J. Immunol., June 15, 2004; 172(12): 7780 - 7790. [Abstract] [Full Text] [PDF]

				Y. Yu, K. S. Moulton, M. K. Khan, S. Vineberg, E. Boye, V. M. Davis, P. E. O'Donnell, J. Bischoff, and D. S. Milstone E-selectin is required for the antiangiogenic activity of endostatin PNAS, May 25, 2004; 101(21): 8005 - 8010. [Abstract] [Full Text] [PDF]

				J. L. Dunne, R. G. Collins, A. L. Beaudet, C. M. Ballantyne, and K. Ley Mac-1, but Not LFA-1, Uses Intercellular Adhesion Molecule-1 to Mediate Slow Leukocyte Rolling in TNF-{alpha}-Induced Inflammation J. Immunol., December 1, 2003; 171(11): 6105 - 6111. [Abstract] [Full Text] [PDF]

				E. S. Ong, X.-P. Gao, N. Xu, D. Predescu, A. Rahman, M. T. Broman, D. H. Jho, and A. B. Malik E. coli pneumonia induces CD18-independent airway neutrophil migration in the absence of increased lung vascular permeability Am J Physiol Lung Cell Mol Physiol, October 1, 2003; 285(4): L879 - L888. [Abstract] [Full Text] [PDF]

				J. Frenette, N. Chbinou, C. Godbout, D. Marsolais, and P. S. Frenette Macrophages, not neutrophils, infiltrate skeletal muscle in mice deficient in P/E selectins after mechanical reloading Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2003; 285(4): R727 - R732. [Abstract] [Full Text] [PDF]

				J.-M. Kiely, Y. Hu, G. Garcia-Cardena, and M. A. Gimbrone Jr. Lipid Raft Localization of Cell Surface E-Selectin Is Required for Ligation-Induced Activation of Phospholipase C{gamma} J. Immunol., September 15, 2003; 171(6): 3216 - 3224. [Abstract] [Full Text] [PDF]

				Y. Katayama, A. Hidalgo, B. C. Furie, D. Vestweber, B. Furie, and P. S. Frenette PSGL-1 participates in E-selectin-mediated progenitor homing to bone marrow: evidence for cooperation between E-selectin ligands and {alpha}4 integrin Blood, September 15, 2003; 102(6): 2060 - 2067. [Abstract] [Full Text] [PDF]

				D. Marshall, J. P. Dangerfield, V. K. Bhatia, K. Y. Larbi, S. Nourshargh, and D. O. Haskard MRL/lpr lupus-prone mice show exaggerated ICAM-1-dependent leucocyte adhesion and transendothelial migration in response to TNF-{alpha} Rheumatology, August 1, 2003; 42(8): 929 - 934. [Abstract] [Full Text] [PDF]

				S. Cuzzocrea, A. Rossi, I. Serraino, E. Mazzon, R. Di Paola, L. Dugo, T. Genovese, B. Calabro, A. P. Caputi, and L. Sautebin 5-Lipoxygenase knockout mice exhibit a resistance to pleurisy and lung injury caused by carrageenan J. Leukoc. Biol., June 1, 2003; 73(6): 739 - 746. [Abstract] [Full Text] [PDF]

				K. Yanaba, Y. Kaburagi, K. Takehara, D. A. Steeber, T. F. Tedder, and S. Sato Relative Contributions of Selectins and Intercellular Adhesion Molecule-1 to Tissue Injury Induced by Immune Complex Deposition Am. J. Pathol., May 1, 2003; 162(5): 1463 - 1473. [Abstract] [Full Text] [PDF]

				M. GOTTE Syndecans in inflammation FASEB J, April 1, 2003; 17(6): 575 - 591. [Abstract] [Full Text] [PDF]

				T. Kadono, G. M. Venturi, D. A. Steeber, and T. F. Tedder Leukocyte Rolling Velocities and Migration Are Optimized by Cooperative L-Selectin and Intercellular Adhesion Molecule-1 Functions J. Immunol., October 15, 2002; 169(8): 4542 - 4550. [Abstract] [Full Text] [PDF]

				P. M. Ellerbroek, A. I. M. Hoepelman, F. Wolbers, J. J. Zwaginga, and F. E. J. Coenjaerts Cryptococcal Glucuronoxylomannan Inhibits Adhesion of Neutrophils to Stimulated Endothelium In Vitro by Affecting Both Neutrophils and Endothelial Cells Infect. Immun., September 1, 2002; 70(9): 4762 - 4771. [Abstract] [Full Text] [PDF]

				L. Piccio, B. Rossi, E. Scarpini, C. Laudanna, C. Giagulli, A. C. Issekutz, D. Vestweber, E. C. Butcher, and G. Constantin Molecular Mechanisms Involved in Lymphocyte Recruitment in Inflamed Brain Microvessels: Critical Roles for P-Selectin Glycoprotein Ligand-1 and Heterotrimeric Gi-Linked Receptors J. Immunol., February 15, 2002; 168(4): 1940 - 1949. [Abstract] [Full Text] [PDF]

				J. L. Dunne, C. M. Ballantyne, A. L. Beaudet, and K. Ley Control of leukocyte rolling velocity in TNF-alpha -induced inflammation by LFA-1 and Mac-1 Blood, January 1, 2002; 99(1): 336 - 341. [Abstract] [Full Text] [PDF]

				O. Fuhrmann, M. Arvand, A. Gohler, M. Schmid, M. Krull, S. Hippenstiel, J. Seybold, C. Dehio, and N. Suttorp Bartonella henselae Induces NF-{kappa}B-Dependent Upregulation of Adhesion Molecules in Cultured Human Endothelial Cells: Possible Role of Outer Membrane Proteins as Pathogenic Factors Infect. Immun., August 1, 2001; 69(8): 5088 - 5097. [Abstract] [Full Text] [PDF]

				P. Kubes and S. M. Kerfoot Leukocyte Recruitment in the Microcirculation: the Rolling Paradigm Revisited Physiology, April 1, 2001; 16(2): 76 - 80. [Abstract] [Full Text] [PDF]

				S. TOHKA, M.-L. LAUKKANEN, S. JALKANEN, and M. SALMI Vascular adhesion protein 1 (VAP-1) functions as a molecular brake during granulocyte rolling and mediates recruitment in vivo FASEB J, February 1, 2001; 15(2): 373 - 382. [Abstract] [Full Text] [PDF]

				J. R. Lindner, M. L. Kahn, S. R. Coughlin, G. R. Sambrano, E. Schauble, D. Bernstein, D. Foy, A. Hafezi-Moghadam, and K. Ley Delayed Onset of Inflammation in Protease-Activated Receptor-2-Deficient Mice J. Immunol., December 1, 2000; 165(11): 6504 - 6510. [Abstract] [Full Text] [PDF]

				E. J. Kunkel, J. L. Dunne, and K. Ley Leukocyte Arrest During Cytokine-Dependent Inflammation In Vivo J. Immunol., March 15, 2000; 164(6): 3301 - 3308. [Abstract] [Full Text] [PDF]

				J. Yang, T. Hirata, K. Croce, G. Merrill-Skoloff, B. Tchernychev, E. Williams, R. Flaumenhaft, B. C. Furie, and B. Furie Targeted Gene Disruption Demonstrates That P-Selectin Glycoprotein Ligand 1 (Psgl-1) Is Required for P-Selectin-Mediated but Not E-Selectin-Mediated Neutrophil Rolling and Migration J. Exp. Med., December 20, 1999; 190(12): 1769 - 1782. [Abstract] [Full Text] [PDF]

				A. S. DE VRIESE, K. ENDLICH, M. ELGER, N. H. LAMEIRE, R. C. ATKINS, H. Y. LAN, A. RUPIN, W. KRIZ, and M. W. STEINHAUSEN The Role of Selectins in Glomerular Leukocyte Recruitment in Rat Anti-Glomerular Basement Membrane Glomerulonephritis J. Am. Soc. Nephrol., December 1, 1999; 10(12): 2510 - 2517. [Abstract] [Full Text]

				D. A. Steeber, M. L. K. Tang, N. E. Green, X.-Q. Zhang, J. E. Sloane, and T. F. Tedder Leukocyte Entry into Sites of Inflammation Requires Overlapping Interactions Between the L-Selectin and ICAM-1 Pathways J. Immunol., August 15, 1999; 163(4): 2176 - 2186. [Abstract] [Full Text] [PDF]

				C. L. Ramos, Y. Huo, U. Jung, S. Ghosh, D. R. Manka, I. J. Sarembock, and K. Ley Direct Demonstration of P-Selectin– and VCAM-1–Dependent Mononuclear Cell Rolling in Early Atherosclerotic Lesions of Apolipoprotein E–Deficient Mice Circ. Res., June 11, 1999; 84(11): 1237 - 1244. [Abstract] [Full Text] [PDF]

				U. Jung and K. Ley Mice Lacking Two or All Three Selectins Demonstrate Overlapping and Distinct Functions for Each Selectin J. Immunol., June 1, 1999; 162(11): 6755 - 6762. [Abstract] [Full Text] [PDF]

				C. Kupatt, H. Habazettl, A. Goedecke, D. A. Wolf, S. Zahler, P. Boekstegers, R. A. Kelly, and B. F. Becker Tumor Necrosis Factor-{alpha} Contributes to Ischemia- and Reperfusion-Induced Endothelial Activation in Isolated Hearts Circ. Res., March 5, 1999; 84(4): 392 - 400. [Abstract] [Full Text] [PDF]