CXCR3 Chemokine Receptor Distribution in Normal and Inflamed Tissues: Expression on Activated Lymphocytes, Endothelial Cells, and Dendritic Cells

Using new human CXCR3 chemokine receptor–specific monoclonal antibodies, we studied human CXCR3 tissue distribution in lymphoid and nonlymphoid organs, as well as in inflammatory conditions, including rheumatoid arthritis, Hashimoto's thyroiditis, and dermal vasculitis. CXCR3 was expressed by certain dendritic cell subsets, specifically myeloid-derived CD11c positive cells, not only in those present in normal lymphoid organs, but also in germinal centers generated in inflammatory conditions. CXCR3 expression was also detected in some lymphocyte subsets such as intraepithelial lymphocytes of secondary lymphoid organs and infiltrating lymphocytes in inflammatory conditions. In addition, CXCR3 was constitutively expressed by endothelial cells (EC) of vessels of medium and large caliber but not in small vessels from different organs. Finally, enhanced CXCR3 expression was found in EC and in infiltrating lymphocytes with an activated phenotype in inflammatory diseases. The CXCR3 chemokine receptor may play a role in the regulation of leukocyte migration to inflammatory sites.

[1]  J. Rodríguez-Frade,et al.  Characterization of antigen-antibody and ligand-receptor interactions , 1996 .

[2]  B. Wolff,et al.  Some aspects of IL‐8 pathophysiology III: chemokine interaction with endothelial cells , 1996, Journal of leukocyte biology.

[3]  C. Schaniel,et al.  The Role of Chemokines in Regulating Cell Migration during Humoral Immune Responses , 1999, Cell.

[4]  F. Sánchez‐Madrid,et al.  Leukocyte polarization in cell migration and immune interactions , 1999, The EMBO journal.

[5]  E. Harlow,et al.  Antibodies: A Laboratory Manual , 1988 .

[6]  D. Jarrossay,et al.  Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon , 1999, Nature Medicine.

[7]  E. Ohlstein,et al.  Chemokine Receptors in Human Endothelial Cells , 1998, The Journal of Biological Chemistry.

[8]  James G. Boyd,et al.  Interferon–inducible T Cell Alpha Chemoattractant (I-TAC): A Novel Non-ELR CXC Chemokine with Potent Activity on Activated T Cells through Selective High Affinity Binding to CXCR3 , 1998, The Journal of experimental medicine.

[9]  H. Augustin,et al.  Endothelial cells differentially express functional CXC-chemokine receptor-4 (CXCR-4/fusin) under the control of autocrine activity and exogenous cytokines. , 1998, Biochemical and biophysical research communications.

[10]  F. Sánchez‐Madrid,et al.  B lymphocyte binding to E- and P-selectins is mediated through the de novo expression of carbohydrates on in vitro and in vivo activated human B cells. , 1994, The Journal of clinical investigation.

[11]  C. Mackay,et al.  The chemokine receptors CXCR3 and CCR5 mark subsets of T cells associated with certain inflammatory reactions. , 1998, The Journal of clinical investigation.

[12]  M. Baggiolini Chemokines and leukocyte traffic , 1998, Nature.

[13]  N. Copeland,et al.  The CC chemokine 6Ckine binds the CXC chemokine receptor CXCR3. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[14]  J. Banchereau,et al.  Dendritic cells capable of stimulating T cells in germinal centres , 1996, Nature.

[15]  C. Martínez-A,et al.  Characterization of the CCR2 chemokine receptor: functional CCR2 receptor expression in B cells. , 1997, Journal of immunology.

[16]  E. Butcher,et al.  Chemokines and the arrest of lymphocytes rolling under flow conditions. , 1998, Science.

[17]  A. Luster,et al.  Chemokines--chemotactic cytokines that mediate inflammation. , 1998, The New England journal of medicine.

[18]  F. Sánchez‐Madrid,et al.  CD43 interacts with moesin and ezrin and regulates its redistribution to the uropods of T lymphocytes at the cell-cell contacts. , 1998, Blood.

[19]  D. Adams,et al.  Leucocyte-endothelial interactions and regulation of leucocyte migration , 1994, The Lancet.

[20]  R. Steinman,et al.  Human blood contains two subsets of dendritic cells, one immunologically mature and the other immature. , 1994, Immunology.

[21]  C. Mackay,et al.  Chemokines and chemokine receptors in T-cell priming and Th1/Th2-mediated responses. , 1998, Immunology today.

[22]  R. Steinman,et al.  Dendritic cells and the control of immunity , 1998, Nature.

[23]  S. Coughlin,et al.  Monocyte chemoattractant protein-1 in human atheromatous plaques. , 1991, The Journal of clinical investigation.

[24]  P. Leder,et al.  The IP-10 chemokine binds to a specific cell surface heparan sulfate site shared with platelet factor 4 and inhibits endothelial cell proliferation , 1995, The Journal of experimental medicine.

[25]  C. Caux,et al.  Regulation of dendritic cell trafficking: a process that involves the participation of selective chemokines , 1999, Journal of leukocyte biology.

[26]  A. Mantovani,et al.  Chemokines , 1994, The Lancet.

[27]  T. Springer Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigm , 1994, Cell.

[28]  H. Kleinman,et al.  Vascular endothelial growth factor and basic fibroblast growth factor induce expression of CXCR4 on human endothelial cells: In vivo neovascularization induced by stromal-derived factor-1alpha. , 1999, The American journal of pathology.

[29]  R. Strieter,et al.  The Role of CXC Chemokines in the Regulation of Angiogenesis in Association with Non-Small-Cell Lung Cancer , 1999 .

[30]  B Dewald,et al.  Human chemokines: an update. , 1997, Annual review of immunology.

[31]  P. Loetscher,et al.  Lymphocyte‐specific chemokine receptor CXCR3: regulation, chemokine binding and gene localization , 1998, European journal of immunology.

[32]  F. Sánchez‐Madrid,et al.  Adhesion molecules from the LFA‐1/ICAM‐1, 3 and VLA‐4/VCAM‐1 pathways on T lymphocytes and vascular endothelium in Graves' and Hashimoto's thyroid glands , 1994, European journal of immunology.

[33]  A. Rot Endothelial cell binding of NAP-1/IL-8: role in neutrophil emigration. , 1992, Immunology today.

[34]  Antonio Lanzavecchia,et al.  Distinct patterns and kinetics of chemokine production regulate dendritic cell function , 1999, European journal of immunology.

[35]  A. Gottlieb,et al.  Detection of a gamma interferon-induced protein IP-10 in psoriatic plaques , 1988, The Journal of experimental medicine.

[36]  A. Huber,et al.  Regulation of transendothelial neutrophil migration by endogenous interleukin-8. , 1991, Science.

[37]  D. Adams,et al.  Proteoglycans on endothelial cells present adhesion-inducing cytokines to leukocytes. , 1993, Immunology today.

[38]  L. Ashman,et al.  Regulation of Endothelial Cell Motility by Complexes of Tetraspan Molecules CD81/TAPA-1 and CD151/PETA-3 with α3β1 Integrin Localized at Endothelial Lateral Junctions , 1998, The Journal of cell biology.

[39]  A. Ben-Baruch,et al.  Chemokines: progress toward identifying molecular targets for therapeutic agents. , 1996, Trends in biotechnology.

[40]  L. Picker,et al.  Lymphocyte Homing and Homeostasis , 1996, Science.

[41]  P. Allavena,et al.  Migration of dendritic cells in response to formyl peptides, C5a, and a distinct set of chemokines. , 1995, Journal of immunology.

[42]  R. Strieter,et al.  The role of CXC chemokines in the regulation of angiogenesis in non-small cell lung cancer. , 1999, Journal of leukocyte biology.

[43]  C. Martínez-A,et al.  The chemokine monocyte chemotactic protein 1 triggers Janus kinase 2 activation and tyrosine phosphorylation of the CCR2B receptor. , 1998, Journal of immunology.