SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on June 28, 2002; DOI 10.1182/blood-2002-03-0841. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-03-0841v1 101/1/38    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Stein, J. V. Articles by Martínez-A., C. Search for Related Content PubMed PubMed Citation Articles by Stein, J. V. Articles by Martínez-A., C. Related Collections Signal Transduction Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 January 2003, Vol. 101, No. 1, pp. 38-44 CHEMOKINES CCR7-mediated physiological lymphocyte homing involves activation of a tyrosine kinase pathway Jens V. Stein, Silvia F. Soriano, Christine M'rini, César Nombela-Arrieta, Gonzalo González de Buitrago, José Miguel Rodríguez-Frade, Mario Mellado, Jean-Philippe Girard, and Carlos Martínez-A. From the Department of Immunology and Oncology, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Cientificas (CSIC), Madrid, Spain; Laboratoire de Physiologie, Faculté de Médecine de Rangueil, Toulouse, France; and Unité de Microscopie Intravitale, Laboratoire de Biologie Vasculaire, Toulouse, France. Homing of blood-borne lymphocytes to peripheral lymph nodes (PLNs) is a multistep process dependent on the sequential engagement of L-selectin, which mediates lymphocyte rolling along the luminal surface of high endothelial venules (HEVs), followed by activation of lymphocyte integrins and transmigration through HEVs. Within lymphoid tissue, B and T lymphocytes then migrate toward specific microenvironments such as B-cell follicles and the paracortex, respectively. The lymphocyte-expressed chemokine receptor CCR7 is playing an important role during this process, as its HEV-presented ligands CCL19 and CCL21 can trigger rapid integrin activation under flow in addition to inducing a chemotactic response, which may participate in transmigration and/or interstitial migration. Here, we report that Tyrphostin (Tyr) AG490, a pharmacological inhibitor of Janus family tyrosine kinases (Jaks), blocked the chemotactic response of primary mouse lymphocytes to CCL19 and CCL21 in a dose-dependent manner. Furthermore, Tyr AG490 inhibited rapid CCL21-mediated up-regulation of 4 and 2 integrin adhesiveness in static adhesion assays and under physiological flow, whereas adhesion induced by phorbol myristate acetate remained unaltered. Using intravital microscopy of subiliac PLNs in mice, we found that adoptively transferred Tyr AG490-treated lymphocytes adhered significantly less in HEVs compared with control cells, although L-selectin-mediated rolling was similar in both samples. Finally, we observed rapid Jak2 phosphorylation in CCL21-stimulated primary mouse lymphocytes. Thus, our study suggests a role for Jak tyrosine kinases during CCR7-mediated lymphocyte recirculation. © 2003 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. Xu, K. Aoyama, M. Kusumoto, A. Matsuzawa, E. C. Butcher, S. A. Michie, T. Matsuyama, and T. Takeuchi Lack of lymphoid chemokines CCL19 and CCL21 enhances allergic airway inflammation in mice Int. Immunol., June 1, 2007; 19(6): 775 - 784. [Abstract] [Full Text] [PDF] D. Garcia-Bernal, E. Sotillo-Mallo, C. Nombela-Arrieta, R. Samaniego, Y. Fukui, J. V. Stein, and J. Teixido DOCK2 is Required for Chemokine-Promoted Human T Lymphocyte Adhesion Under Shear Stress Mediated by the Integrin {alpha}4beta1 J. Immunol., October 15, 2006; 177(8): 5215 - 5225. [Abstract] [Full Text] [PDF] N. Sanchez-Sanchez, L. Riol-Blanco, and J. L. Rodriguez-Fernandez The Multiple Personalities of the Chemokine Receptor CCR7 in Dendritic Cells J. Immunol., May 1, 2006; 176(9): 5153 - 5159. [Abstract] [Full Text] [PDF] V. Carriere, R. Colisson, C. Jiguet-Jiglaire, E. Bellard, G. Bouche, T. Al Saati, F. Amalric, J.-P. Girard, and C. M'Rini Cancer Cells Regulate Lymphocyte Recruitment and Leukocyte-Endothelium Interactions in the Tumor-Draining Lymph Node Cancer Res., December 15, 2005; 65(24): 11639 - 11648. [Abstract] [Full Text] [PDF] D. H. Walter, J. Haendeler, J. Reinhold, U. Rochwalsky, F. Seeger, J. Honold, J. Hoffmann, C. Urbich, R. Lehmann, F. Arenzana-Seisdesdos, et al. Impaired CXCR4 Signaling Contributes to the Reduced Neovascularization Capacity of Endothelial Progenitor Cells From Patients With Coronary Artery Disease Circ. Res., November 25, 2005; 97(11): 1142 - 1151. [Abstract] [Full Text] [PDF] D. Garcia-Bernal, N. Wright, E. Sotillo-Mallo, C. Nombela-Arrieta, J. V. Stein, X. R. Bustelo, and J. Teixido Vav1 and Rac Control Chemokine-promoted T Lymphocyte Adhesion Mediated by the Integrin {alpha}4{beta}1 Mol. Biol. Cell, July 1, 2005; 16(7): 3223 - 3235. [Abstract] [Full Text] [PDF] M. Moriguchi, B. D. Hissong, M. Gadina, K. Yamaoka, H. L. Tiffany, P. M. Murphy, F. Candotti, and J. J. O'Shea CXCL12 Signaling Is Independent of Jak2 and Jak3 J. Biol. Chem., April 29, 2005; 280(17): 17408 - 17414. [Abstract] [Full Text] [PDF] C. C. Schimanski, S. Schwald, N. Simiantonaki, C. Jayasinghe, U. Gonner, V. Wilsberg, T. Junginger, M. R. Berger, P. R. Galle, and M. Moehler Effect of Chemokine Receptors CXCR4 and CCR7 on the Metastatic Behavior of Human Colorectal Cancer Clin. Cancer Res., March 1, 2005; 11(5): 1743 - 1750. [Abstract] [Full Text] [PDF] S. S. Li, A. Forslow, and K.-G. Sundqvist Autocrine Regulation of T Cell Motility by Calreticulin-Thrombospondin-1 Interaction J. Immunol., January 15, 2005; 174(2): 654 - 661. [Abstract] [Full Text] [PDF] A. P. Martin, E. C. Coronel, G.-i. Sano, S.-C. Chen, G. Vassileva, C. Canasto-Chibuque, J. D. Sedgwick, P. S. Frenette, M. Lipp, G. C. Furtado, et al. A Novel Model for Lymphocytic Infiltration of the Thyroid Gland Generated by Transgenic Expression of the CC Chemokine CCL21 J. Immunol., October 15, 2004; 173(8): 4791 - 4798. [Abstract] [Full Text] [PDF] N. Sanchez-Sanchez, L. Riol-Blanco, G. de la Rosa, A. Puig-Kroger, J. Garcia-Bordas, D. Martin, N. Longo, A. Cuadrado, C. Cabanas, A. L. Corbi, et al. Chemokine receptor CCR7 induces intracellular signaling that inhibits apoptosis of mature dendritic cells Blood, August 1, 2004; 104(3): 619 - 625. [Abstract] [Full Text] [PDF] E. Scandella, Y. Men, D. F. Legler, S. Gillessen, L. Prikler, B. Ludewig, and M. Groettrup CCL19/CCL21-triggered signal transduction and migration of dendritic cells requires prostaglandin E2 Blood, March 1, 2004; 103(5): 1595 - 1601. [Abstract] [Full Text] [PDF]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020