|
|
Prepublished online as a Blood First Edition Paper on February 27, 2003; DOI 10.1182/blood-2002-06-1782.
 Previous Article | Table of Contents | Next Article 
Blood, 1 June 2003, Vol. 101, No. 11, pp. 4245-4252
CHEMOKINES
L-selectin stimulation enhances functional expression of surface CXCR4 in lymphocytes: implications for cellular activation during adhesion and migration
Ziqiang Ding,
Thomas B. Issekutz,
Gregory P. Downey, and
Thomas K. Waddell
From the Division of Thoracic Surgery, Department of Surgery; Division of Respirology, Department of Medicine, Toronto General Research Institute of the University Health Network, University of Toronto, ON, Canada; and Department of Pediatrics, Division of Immunology, Rheumatology and Infectious Diseases, IWK Grace Health Center, Halifax, NS, Canada.
L-selectin mediates leukocyte tethering and rolling, the first step in a sequential process of leukocyte adhesion and migration. Additionally, L-selectin has important signaling roles perhaps contributing to leukocyte activation and integrin-mediated adhesion. Because chemokines are critically involved in leukocyte activation, we questioned whether L-selectin signaling affects chemokine receptor expression and function. We observed that whereas only 5% to 15% of freshly isolated lymphocytes expressed CXCR4 on the cell surface, intracellular CXCR4 was detectable in all cells. Engagement of L-selectin by antibody cross-linking or the L-selectin ligands fucoidan or sulfatide mobilized intracellular CXCR4 to significantly increase surface CXCR4 expression but did not affect CCR5, CCR7, or  2-integrin expression. L-selectin stimulation also inhibited stromal-derived factor 1 (SDF-1)–induced CXCR4 internalization. The combined effects of L-selectin on CXCR4 trafficking are likely important in markedly enhancing cell activation by SDF-1. Blockade of SDF-1–induced CXCR4 internalization resulted in enhanced actin polymerization on subsequent exposure to SDF-1. Physiologically more important, L-selectin stimulation increased SDF-1–induced lymphocyte adhesion and transendothelial migration, which were inhibited by anti–leukocyte function-associated antigen 1 antibodies, tyrosine kinase inhibitors, and pertussis toxin. To further corroborate the additive stimulating effects, L-selectin signaling and SDF-1 increased 2-integrin activation. Taken together, L-selectin–mediated signals specifically enhance CXCR4 expression and function, suggesting a novel mechanism for the modulation of lymphocyte activation during cell adhesion and transmigration.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
H. T. Ngo, X. Leleu, J. Lee, X. Jia, M. Melhem, J. Runnels, A.-S. Moreau, N. Burwick, A. K. Azab, A. Roccaro, et al.
SDF-1/CXCR4 and VLA-4 interaction regulates homing in Waldenstrom macroglobulinemia
Blood,
July 1, 2008;
112(1):
150 - 158.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Richards, M. P. Longhi, K. Wright, A. Gallimore, and A. Ager
CD62L (L-Selectin) Down-Regulation Does Not Affect Memory T Cell Distribution but Failure to Shed Compromises Anti-Viral Immunity
J. Immunol.,
January 1, 2008;
180(1):
198 - 206.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Masztalerz, I. S. Zeelenberg, Y. M. Wijnands, R. de Bruijn, A. M. Drager, H. Janssen, and E. Roos
Synaptotagmin 3 deficiency in T cells impairs recycling of the chemokine receptor CXCR4 and thereby inhibits CXCL12 chemokine-induced migration
J. Cell Sci.,
January 15, 2007;
120(2):
219 - 228.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Kucia, R. Reca, K. Miekus, J. Wanzeck, W. Wojakowski, A. Janowska-Wieczorek, J. Ratajczak, and M. Z. Ratajczak
Trafficking of Normal Stem Cells and Metastasis of Cancer Stem Cells Involve Similar Mechanisms: Pivotal Role of the SDF-1-CXCR4 Axis
Stem Cells,
August 1, 2005;
23(7):
879 - 894.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. D. Belanger and Y. St-Pierre
Role of selectins in the triggering, growth, and dissemination of T-lymphoma cells: implication of L-selectin in the growth of thymic lymphoma
Blood,
June 15, 2005;
105(12):
4800 - 4806.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. D. Rosen, D. Tsay, M. S. Singer, S. Hemmerich, and W. M. Abraham
Therapeutic Targeting of Endothelial Ligands for L-selectin (PNAd) in a Sheep Model of Asthma
Am. J. Pathol.,
March 1, 2005;
166(3):
935 - 944.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Atarashi, T. Hirata, M. Matsumoto, N. Kanemitsu, and M. Miyasaka
Rolling of Th1 Cells via P-Selectin Glycoprotein Ligand-1 Stimulates LFA-1-Mediated Cell Binding to ICAM-1
J. Immunol.,
February 1, 2005;
174(3):
1424 - 1432.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Wysoczynski, R. Reca, J. Ratajczak, M. Kucia, N. Shirvaikar, M. Honczarenko, M. Mills, J. Wanzeck, A. Janowska-Wieczorek, and M. Z. Ratajczak
Incorporation of CXCR4 into membrane lipid rafts primes homing-related responses of hematopoietic stem/progenitor cells to an SDF-1 gradient
Blood,
January 1, 2005;
105(1):
40 - 48.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Hidalgo, A. J. Peired, L. A. Weiss, Y. Katayama, and P. S. Frenette
The integrin {alpha}M{beta}2 anchors hematopoietic progenitors in the bone marrow during enforced mobilization
Blood,
August 15, 2004;
104(4):
993 - 1001.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. D. van Buul and P. L. Hordijk
Signaling in Leukocyte Transendothelial Migration
Arterioscler. Thromb. Vasc. Biol.,
May 1, 2004;
24(5):
824 - 833.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
M. Hamon, E. Mbemba, N. Charnaux, H. Slimani, S. Brule, L. Saffar, R. Vassy, C. Prost, N. Lievre, A. Starzec, et al.
A syndecan-4/CXCR4 complex expressed on human primary lymphocytes and macrophages and HeLa cell line binds the CXC chemokine stromal cell-derived factor-1 (SDF-1)
Glycobiology,
April 1, 2004;
14(4):
311 - 323.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Letsch, U. Keilholz, G. Assfalg, V. Mailander, E. Thiel, and C. Scheibenbogen
Bone Marrow Contains Melanoma-reactive CD8+ Effector T Cells and, Compared with Peripheral Blood, Enriched Numbers of Melanoma-reactive CD8+ Memory T Cells
Cancer Res.,
September 1, 2003;
63(17):
5582 - 5586.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
