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*
Max Delbrück Center for Molecular Medicine, Berlin-Buch;
GSF-National Research Center for Environment and Health, Institute of Immunology, Munich;
GSF-National Research Center for Environment and Health, Institute of Molecular Virology, Neuherberg, Oberschleissheim; and
§
Department of Hematology and Oncology, Städtisches Krankenhaus München-Schwabing, Munich, Germany
We describe the expression and regulation of the HIV-1 coreceptor
CXCR4/fusin. Using anti-CXCR4 mAb, we demonstrate that this
chemokine receptor is highly expressed on neutrophils, monocytes, B
cells, and naive T cells among peripheral blood cells. In secondary
lymphoid organs CXCR4 was found to be expressed on B cells. However,
individual variations with regard to surface expression could be
observed on T cells. Expression of the receptor is not confined to the
cell surface, as large amounts of intracellular stores can be found on
various leukocytes. Upon activation with phorbol esters the amount of
cell surface-expressed CXCR4 on lymphocytes increases twofold within
30 s before it is completely down-regulated within the next 2 min.
Incubation of leukocytes with stroma derived factor-1
, the natural
ligand for CXCR4, induces down-regulation of up to 60% of
surface-expressed receptors in a pertussis toxin-insensitive manner.
Interestingly, receptor cross-linking caused by incubation of cells
with anti-CXCR4 mAb triggers receptor trafficking, in that the
receptor is rapidly internalized and recycled to the cell surface.
Therefore, receptor internalization and recycling may regulate the
functional interaction of the receptor with envelope proteins during an
initial step of HIV-1 infection.
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H. Nagase, M. Miyamasu, M. Yamaguchi, M. Imanishi, N. H. Tsuno, K. Matsushima, K. Yamamoto, Y. Morita, and K. Hirai Cytokine-mediated regulation of CXCR4 expression in human neutrophils J. Leukoc. Biol., April 1, 2002; 71(4): 711 - 717. [Abstract] [Full Text] [PDF]
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U. E. Hopken, H.-D. Foss, D. Meyer, M. Hinz, K. Leder, H. Stein, and M. Lipp Up-regulation of the chemokine receptor CCR7 in classical but not in lymphocyte-predominant Hodgkin disease correlates with distinct dissemination of neoplastic cells in lymphoid organs Blood, February 15, 2002; 99(4): 1109 - 1116. [Abstract] [Full Text] [PDF]
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J. Cashman, I. Clark-Lewis, A. Eaves, and C. Eaves Stromal-derived factor 1 inhibits the cycling of very primitive human hematopoietic cells in vitro and in NOD/SCID mice Blood, February 1, 2002; 99(3): 792 - 799. [Abstract] [Full Text] [PDF]
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A. Marchese and J. L. Benovic Agonist-promoted Ubiquitination of the G Protein-coupled Receptor CXCR4 Mediates Lysosomal Sorting J. Biol. Chem., November 30, 2001; 276(49): 45509 - 45512. [Abstract] [Full Text] [PDF]
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N. Zhou, Z. Luo, J. Luo, D. Liu, J. W. Hall, R. J. Pomerantz, and Z. Huang Structural and Functional Characterization of Human CXCR4 as a Chemokine Receptor and HIV-1 Co-receptor by Mutagenesis and Molecular Modeling Studies J. Biol. Chem., November 9, 2001; 276(46): 42826 - 42833. [Abstract] [Full Text] [PDF]
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H. Geminder, O. Sagi-Assif, L. Goldberg, T. Meshel, G. Rechavi, I. P. Witz, and A. Ben-Baruch A Possible Role for CXCR4 and Its Ligand, the CXC Chemokine Stromal Cell-Derived Factor-1, in the Development of Bone Marrow Metastases in Neuroblastoma J. Immunol., October 15, 2001; 167(8): 4747 - 4757. [Abstract] [Full Text] [PDF]
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S. K. Gupta, K. Pillarisetti, and N. Aiyar CXCR4 undergoes complex lineage and inducing agent-dependent dissociation of expression and functional responsiveness to SDF-1{alpha} during myeloid differentiation J. Leukoc. Biol., September 1, 2001; 70(3): 431 - 438. [Abstract] [Full Text] [PDF]
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I. Tchou, L. Misery, O. Sabido, C. Dezutter-Dambuyant, T. Bourlet, P. Moja, H. Hamzeh, J. Peguet-Navarro, D. Schmitt, and C. Genin Functional HIV CXCR4 coreceptor on human epithelial Langerhans cells and infection by HIV strain X4 J. Leukoc. Biol., August 1, 2001; 70(2): 313 - 321. [Abstract] [Full Text] [PDF]
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F. Bautz, C. Denzlinger, L. Kanz, and R. Mohle Chemotaxis and transendothelial migration of CD34+ hematopoietic progenitor cells induced by the inflammatory mediator leukotriene D4 are mediated by the 7-transmembrane receptor CysLT1 Blood, June 1, 2001; 97(11): 3433 - 3440. [Abstract] [Full Text] [PDF]
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R. Guerriero, G. Mattia, U. Testa, C. Chelucci, G. Macioce, I. Casella, P. Samoggia, C. Peschle, and H. J. Hassan Stromal cell-derived factor 1{alpha} increases polyploidization of megakaryocytes generated by human hematopoietic progenitor cells Blood, May 1, 2001; 97(9): 2587 - 2595. [Abstract] [Full Text] [PDF]
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L. M. Ebert and S. R. McColl Coregulation of CXC Chemokine Receptor and CD4 Expression on T Lymphocytes During Allogeneic Activation J. Immunol., April 15, 2001; 166(8): 4870 - 4878. [Abstract] [Full Text] [PDF]
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C. Buri, M. Korner, P. Scharli, D. Cefai, M. Uguccioni, C. Mueller, J. A. Laissue, and L. Mazzucchelli CC chemokines and the receptors CCR3 and CCR5 are differentially expressed in the nonneoplastic leukocytic infiltrates of Hodgkin disease Blood, March 15, 2001; 97(6): 1543 - 1548. [Abstract] [Full Text] [PDF]
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S. Shalekoff and C. T. Tiemessen Duration of Sample Storage Dramatically Alters Expression of the Human Immunodeficiency Virus Coreceptors CXCR4 and CCR5 Clin. Vaccine Immunol., March 1, 2001; 8(2): 432 - 436. [Abstract] [Full Text] [PDF]
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R. P. Cherla and R. K. Ganju Stromal Cell-Derived Factor 1{{alpha}}-Induced Chemotaxis in T Cells Is Mediated by Nitric Oxide Signaling Pathways J. Immunol., March 1, 2001; 166(5): 3067 - 3074. [Abstract] [Full Text] [PDF]
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A. R. L. Gear, S. Suttitanamongkol, D. Viisoreanu, R. K. Polanowska-Grabowska, S. Raha, and D. Camerini Adenosine diphosphate strongly potentiates the ability of the chemokines MDC, TARC, and SDF-1 to stimulate platelet function Blood, February 15, 2001; 97(4): 937 - 945. [Abstract] [Full Text] [PDF]
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M. L. Colamussi, P. Secchiero, A. Gonelli, M. Marchisio, G. Zauli, and S. Capitani Stromal derived factor-1{alpha} (SDF-1{alpha}) induces CD4+ T cell apoptosis via the functional up-regulation of the Fas (CD95)/Fas ligand (CD95L) pathway J. Leukoc. Biol., February 1, 2001; 69(2): 263 - 270. [Abstract] [Full Text]
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R. D. Chernock, R. P. Cherla, and R. K. Ganju SHP2 and cbl participate in {alpha}-chemokine receptor CXCR4-mediated signaling pathways Blood, February 1, 2001; 97(3): 608 - 615. [Abstract] [Full Text] [PDF]
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T. Nanki, K. Hayashida, H. S. El-Gabalawy, S. Suson, K. Shi, H. J. Girschick, S. Yavuz, and P. E. Lipsky Stromal Cell-Derived Factor-1-CXC Chemokine Receptor 4 Interactions Play a Central Role in CD4+ T Cell Accumulation in Rheumatoid Arthritis Synovium J. Immunol., December 1, 2000; 165(11): 6590 - 6598. [Abstract] [Full Text] [PDF]
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I. J. Crane, C. A. Wallace, S. McKillop-Smith, and J. V. Forrester CXCR4 Receptor Expression on Human Retinal Pigment Epithelial Cells from the Blood-Retina Barrier Leads to Chemokine Secretion and Migration in Response to Stromal Cell-Derived Factor 1{alpha} J. Immunol., October 15, 2000; 165(8): 4372 - 4378. [Abstract] [Full Text] [PDF]
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T.-J. Lin, T. B. Issekutz, and J. S. Marshall Human Mast Cells Transmigrate Through Human Umbilical Vein Endothelial Monolayers and Selectively Produce IL-8 in Response to Stromal Cell-Derived Factor-1{alpha} J. Immunol., July 1, 2000; 165(1): 211 - 220. [Abstract] [Full Text] [PDF]
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H. Nagase, M. Miyamasu, M. Yamaguchi, T. Fujisawa, K. Ohta, K. Yamamoto, Y. Morita, and K. Hirai Expression of CXCR4 in Eosinophils: Functional Analyses and Cytokine-Mediated Regulation J. Immunol., June 1, 2000; 164(11): 5935 - 5943. [Abstract] [Full Text] [PDF]
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T. Nanki and P. E. Lipsky Cutting Edge: Stromal Cell-Derived Factor-1 Is a Costimulator for CD4+ T Cell Activation J. Immunol., May 15, 2000; 164(10): 5010 - 5014. [Abstract] [Full Text] [PDF]
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P. Secchiero, D. Zella, S. Curreli, P. Mirandola, S. Capitani, R. C. Gallo, and G. Zauli Engagement of CD28 Modulates CXC Chemokine Receptor 4 Surface Expression in Both Resting and CD3-Stimulated CD4+ T Cells J. Immunol., April 15, 2000; 164(8): 4018 - 4024. [Abstract] [Full Text] [PDF]
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D. Daelemans, D. Schols, M. Witvrouw, C. Pannecouque, S. Hatse, S. van Dooren, F. Hamy, T. Klimkait, E. de Clercq, and A.-M. VanDamme A Second Target for the Peptoid Tat/Transactivation Response Element Inhibitor CGP64222: Inhibition of Human Immunodeficiency Virus Replication by Blocking CXC-Chemokine Receptor 4-Mediated Virus Entry Mol. Pharmacol., January 1, 2000; 57(1): 116 - 124. [Abstract] [Full Text]
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Y. Sotsios, G. C. Whittaker, J. Westwick, and S. G. Ward The CXC Chemokine Stromal Cell-Derived Factor Activates a Gi-Coupled Phosphoinositide 3-Kinase in T Lymphocytes J. Immunol., December 1, 1999; 163(11): 5954 - 5963. [Abstract] [Full Text] [PDF]
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J. A. Burger, M. Burger, and T. J. Kipps Chronic Lymphocytic Leukemia B Cells Express Functional CXCR4 Chemokine Receptors That Mediate Spontaneous Migration Beneath Bone Marrow Stromal Cells Blood, December 1, 1999; 94(11): 3658 - 3667. [Abstract] [Full Text] [PDF]
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M. Honczarenko, R. S. Douglas, C. Mathias, B. Lee, M. Z. Ratajczak, and L. E. Silberstein SDF-1 Responsiveness Does Not Correlate With CXCR4 Expression Levels of Developing Human Bone Marrow B Cells Blood, November 1, 1999; 94(9): 2990 - 2998. [Abstract] [Full Text] [PDF]
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 C. Abbal, P. Jourdan, T. Hori, J. Bousquet, H. Yssel, and J. Pene TCR-mediated activation of allergen-specific CD45RO+ memory T lymphocytes results in down-regulation of cell-surface CXCR4 expression and a strongly reduced capacity to migrate in response to stromal cell-derived factor-1 Int. Immunol., September 1, 1999; 11(9): 1451 - 1462. [Abstract] [Full Text] [PDF]
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N. Zimmermann, J. J. Conkright, and M. E. Rothenberg CC Chemokine Receptor-3 Undergoes Prolonged Ligand-induced Internalization J. Biol. Chem., April 30, 1999; 274(18): 12611 - 12618. [Abstract] [Full Text] [PDF]
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D. Misse, M. Cerutti, N. Noraz, P. Jourdan, J. Favero, G. Devauchelle, H. Yssel, N. Taylor, and F. Veas A CD4-Independent Interaction of Human Immunodeficiency Virus-1 gp120 With CXCR4 Induces Their Cointernalization, Cell Signaling, and T-Cell Chemotaxis Blood, April 15, 1999; 93(8): 2454 - 2462. [Abstract] [Full Text] [PDF]
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 R. Salcedo, K. Wasserman, H. A. Young, M. C. Grimm, O. M. Z. Howard, M. R. Anver, H. K. Kleinman, W. J. Murphy, and J. J. Oppenheim Vascular Endothelial Growth Factor and Basic Fibroblast Growth Factor Induce Expression of CXCR4 on Human Endothelial Cells : In Vivo Neovascularization Induced byStromal-Derived Factor-1{alpha} Am. J. Pathol., April 1, 1999; 154(4): 1125 - 1135. [Abstract] [Full Text] [PDF]
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S. W. Cole, B. D. Jamieson, and J. A. Zack cAMP Up-Regulates Cell Surface Expression of Lymphocyte CXCR4: Implications for Chemotaxis and HIV-1 Infection J. Immunol., February 1, 1999; 162(3): 1392 - 1400. [Abstract] [Full Text] [PDF]
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J. W. Peacock and F. R. Jirik TCR Activation Inhibits Chemotaxis Toward Stromal Cell-Derived Factor-1: Evidence for Reciprocal Regulation Between CXCR4 and the TCR J. Immunol., January 1, 1999; 162(1): 215 - 223. [Abstract] [Full Text] [PDF]
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P. Secchiero, D. Zella, O. Barabitskaja, M. S. Reitz, S. Capitani, R. C. Gallo, and G. Zauli Progressive and Persistent Downregulation of Surface CXCR4 in CD4+ T Cells Infected With Human Herpesvirus 7 Blood, December 15, 1998; 92(12): 4521 - 4528. [Abstract] [Full Text] [PDF]
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J. L. Riley, B. L. Levine, N. Craighead, T. Francomano, D. Kim, R. G. Carroll, and C. H. June Naive and Memory CD4 T Cells Differ in Their Susceptibilities to Human Immunodeficiency Virus Type 1 Infection following CD28 Costimulation: Implications for Transmission and Pathogenesis J. Virol., October 1, 1998; 72(10): 8273 - 8280. [Abstract] [Full Text] [PDF]
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R. K. Ganju, S. A. Brubaker, J. Meyer, P. Dutt, Y. Yang, S. Qin, W. Newman, and J. E. Groopman The alpha -Chemokine, Stromal Cell-derived Factor-1alpha , Binds to the Transmembrane G-protein-coupled CXCR-4 Receptor and Activates Multiple Signal Transduction Pathways J. Biol. Chem., September 4, 1998; 273(36): 23169 - 23175. [Abstract] [Full Text] [PDF]
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 Q. Ma, D. Jones, P. R. Borghesani, R. A. Segal, T. Nagasawa, T. Kishimoto, R. T. Bronson, and T. A. Springer Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice PNAS, August 4, 1998; 95(16): 9448 - 9453. [Abstract] [Full Text] [PDF]
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 N Signoret, M. Rosenkilde, P. Klasse, T. Schwartz, M. Malim, J. Hoxie, and M Marsh Differential regulation of CXCR4 and CCR5 endocytosis J. Cell Sci., January 9, 1998; 111(18): 2819 - 2830. [Abstract] [PDF]
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P. Loetscher, A. Pellegrino, J.-H. Gong, I. Mattioli, M. Loetscher, G. Bardi, M. Baggiolini, and I. Clark-Lewis The Ligands of CXC Chemokine Receptor 3, I-TAC, Mig, and IP10, Are Natural Antagonists for CCR3 J. Biol. Chem., January 26, 2001; 276(5): 2986 - 2991. [Abstract] [Full Text] [PDF]
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