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PMID: 11134180 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Cell cycle-dependent expression of CXC chemokine receptor 3 by endothelial cells mediates angiostatic activity.

The Journal of clinical investigation ·Vol. 107 ·No. 1 ·2001-01-00 ·Pages 53-63

Romagnani P, Annunziato F, Lasagni L, Lazzeri E, Beltrame C, Francalanci M, Uguccioni M, Galli G, Cosmi L, Maurenzig L, Baggiolini M, Maggi E, Romagnani S, Serio M

Abstract

Endothelial cell receptors for the angiostatic chemokines IFN-gamma-inducible protein of 10 kDa (IP-10) and monokine induced by IFN-gamma (Mig) have not yet been identified, and the mechanisms responsible for the effects of these chemokines on angiogenesis are still unclear. IP-10 and Mig share a common functional receptor on activated T lymphocytes, named CXC chemokine receptor 3 (CXCR3). Using in situ hybridization and immunohistochemistry, we show that CXCR3 is expressed by a small percentage of microvascular endothelial cells in several human normal and pathological tissues. Primary cultures of human microvascular endothelial cells (HMVECs) likewise express CXCR3, although this expression is limited to the S/G2-M phase of their cell cycle. Both IP-10 and Mig, as well as the IFN-gamma-inducible T-cell alpha chemoattractant (I-TAC), which all share high-affinity binding for CXCR3, block HMVEC proliferation in vitro, an effect that can be inhibited by an anti-CXCR3 antibody. These data provide definitive evidence of CXCR3 expression by HMVEC and open new avenues for therapeutic interventions in all conditions in which an angiostatic effect may be beneficial.

MeSH Terms
Angiogenesis Inhibitors/pharmacology Cell Cycle Cell Division/drug effects Cells, Cultured Chemokine CXCL10 Chemokine CXCL11 Chemokine CXCL9 Chemokines, CXC/pharmacology Endothelium, Vascular/cytology,drug effects,metabolism Gene Expression Humans Intercellular Signaling Peptides and Proteins Neovascularization, Physiologic RNA, Messenger/genetics,metabolism Receptors, CXCR3 Receptors, Chemokine/antagonists & inhibitors,genetics,metabolism Tissue Distribution
Chemicals
Angiogenesis Inhibitors CXCL11 protein, human CXCL9 protein, human CXCR3 protein, human Chemokine CXCL10 Chemokine CXCL11 Chemokine CXCL9 Chemokines, CXC Intercellular Signaling Peptides and Proteins RNA, Messenger Receptors, CXCR3 Receptors, Chemokine
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Romagnani P
Department of Clinical Pathophysiology, Endocrinology Unit, University of Florence, Florence, Italy. promagnani@iol.it
Annunziato F
Lasagni L
Lazzeri E
Beltrame C
Francalanci M
Uguccioni M
Galli G
Cosmi L
Maurenzig L
Baggiolini M
Maggi E
Romagnani S
Serio M
References (40)
40 references, click to expand
  1. Role for interactions between IP-10/Mig and CXCR3 in proliferative glomerulonephritis.
    J Am Soc Nephrol. 1999 Dec;10(12):2518-26 PMID: 10589690
  2. Differential expression of three T lymphocyte-activating CXC chemokines by human atheroma-associated cells.
    J Clin Invest. 1999 Oct;104(8):1041-50 PMID: 10525042
  3. Macrophage-derived chemokine and EBI1-ligand chemokine attract human thymocytes in different stage of development and are produced by distinct subsets of medullary epithelial cells: possible implications for negative selection.
    J Immunol. 2000 Jul 1;165(1):238-46 PMID: 10861057
  4. CXC chemokine receptor 3 expression on CD34(+) hematopoietic progenitors from human cord blood induced by granulocyte-macrophage colony-stimulating factor: chemotaxis and adhesion induced by its ligands, interferon gamma-inducible protein 10 and monokine induced by interferon gamma.
    Blood. 2000 Aug 15;96(4):1230-8 PMID: 10942362
  5. Differential expression and responsiveness of chemokine receptors (CXCR1-3) by human microvascular endothelial cells and umbilical vein endothelial cells.
    FASEB J. 2000 Oct;14(13):2055-64 PMID: 11023990
  6. The proliferation of capillary endothelial cells.
    Cancer Res. 1972 Jan;32(1):77-82 PMID: 5007690
  7. Macrophages, wound repair and angiogenesis.
    Prog Clin Biol Res. 1988;266:131-45 PMID: 2454496
  8. Platelet factor 4 blocks the binding of basic fibroblast growth factor to the receptor and inhibits the spontaneous migration of vascular endothelial cells.
    Biochem Biophys Res Commun. 1990 Oct 30;172(2):595-600 PMID: 2173572
  9. Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor.
    Cell. 1991 Feb 22;64(4):841-8 PMID: 1847668
  10. Relation of neovascularisation to metastasis of non-small-cell lung cancer.
    Lancet. 1992 Jul 18;340(8812):145-6 PMID: 1378165
  11. Ability of HIV to promote a TH1 to TH0 shift and to replicate preferentially in TH2 and TH0 cells.
    Science. 1994 Jul 8;265(5169):244-8 PMID: 8023142
  12. Inhibition of endothelial cell proliferation by platelet factor-4 involves a unique action on S phase progression.
    J Cell Biol. 1994 Nov;127(4):1121-7 PMID: 7962072
  13. Interferon-alpha and interferon-gamma down-regulate the production of interleukin-8 and ENA-78 in human monocytes.
    J Leukoc Biol. 1995 Jun;57(6):929-35 PMID: 7790776
  14. Human interferon-inducible protein 10 is a potent inhibitor of angiogenesis in vivo.
    J Exp Med. 1995 Jul 1;182(1):155-62 PMID: 7540647
  15. The IP-10 chemokine binds to a specific cell surface heparan sulfate site shared with platelet factor 4 and inhibits endothelial cell proliferation.
    J Exp Med. 1995 Jul 1;182(1):219-31 PMID: 7790818
  16. The functional role of the ELR motif in CXC chemokine-mediated angiogenesis.
    J Biol Chem. 1995 Nov 10;270(45):27348-57 PMID: 7592998
  17. Angiogenesis in cancer, vascular, rheumatoid and other disease.
    Nat Med. 1995 Jan;1(1):27-31 PMID: 7584949
  18. Modulation of transforming growth factor beta receptor levels on microvascular endothelial cells during in vitro angiogenesis.
    J Clin Invest. 1996 Mar 15;97(6):1436-46 PMID: 8617876
  19. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis.
    Cell. 1996 Aug 9;86(3):353-64 PMID: 8756718
  20. Interferon-inducible protein-10 involves vascular smooth muscle cell migration, proliferation, and inflammatory response.
    J Biol Chem. 1996 Sep 27;271(39):24286-93 PMID: 8798675
  21. Chemokine receptor specific for IP10 and mig: structure, function, and expression in activated T-lymphocytes.
    J Exp Med. 1996 Sep 1;184(3):963-9 PMID: 9064356
  22. Phase I trial of recombinant platelet factor 4 (rPF4) in patients with advanced colorectal carcinoma.
    Invest New Drugs. 1996;14(4):387-9 PMID: 9157074
  23. Chemokines.
    Blood. 1997 Aug 1;90(3):909-28 PMID: 9242519
  24. The role of CXC chemokines in the regulation of angiogenesis in non-small cell lung cancer.
    J Leukoc Biol. 1997 Nov;62(5):554-62 PMID: 9365108
  25. Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s.
    J Exp Med. 1998 Jan 5;187(1):129-34 PMID: 9419219
  26. Chemokine receptors in human endothelial cells. Functional expression of CXCR4 and its transcriptional regulation by inflammatory cytokines.
    J Biol Chem. 1998 Feb 13;273(7):4282-7 PMID: 9461627
  27. The chemokine receptors CXCR3 and CCR5 mark subsets of T cells associated with certain inflammatory reactions.
    J Clin Invest. 1998 Feb 15;101(4):746-54 PMID: 9466968
  28. Chemokines and leukocyte traffic.
    Nature. 1998 Apr 9;392(6676):565-8 PMID: 9560152
  29. High CD30 ligand expression by epithelial cells and Hassal's corpuscles in the medulla of human thymus.
    Blood. 1998 May 1;91(9):3323-32 PMID: 9558389
  30. The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract.
    Nature. 1998 Jun 11;393(6685):591-4 PMID: 9634237
  31. Endothelial cells differentially express functional CXC-chemokine receptor-4 (CXCR-4/fusin) under the control of autocrine activity and exogenous cytokines.
    Biochem Biophys Res Commun. 1998 Jun 9;247(1):38-45 PMID: 9636650
  32. The CC chemokine 6Ckine binds the CXC chemokine receptor CXCR3.
    Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):8205-10 PMID: 9653165
  33. Inhibition of human umbilical vein endothelial cell proliferation by the CXC chemokine, platelet factor 4 (PF4), is associated with impaired downregulation of p21(Cip1/WAF1).
    Blood. 1999 Jan 1;93(1):25-33 PMID: 9864142
  34. Highly sensitive and specific fluorescence reverse transcription-PCR assay for the pseudogene-free detection of beta-actin transcripts as quantitative reference.
    Clin Chem. 1999 Feb;45(2):297-300 PMID: 9931059
  35. Cutting edge: species specificity of the CC chemokine 6Ckine signaling through the CXC chemokine receptor CXCR3: human 6Ckine is not a ligand for the human or mouse CXCR3 receptors.
    J Immunol. 1999 Apr 1;162(7):3765-9 PMID: 10201891
  36. Chemokine receptor responses on T cells are achieved through regulation of both receptor expression and signaling.
    J Immunol. 1999 Apr 1;162(7):3840-50 PMID: 10201901
  37. 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.
    Am J Pathol. 1999 Apr;154(4):1125-35 PMID: 10233851
  38. The chemokine receptor CXCR3 is expressed on malignant B cells and mediates chemotaxis.
    J Clin Invest. 1999 Jul;104(1):115-21 PMID: 10393705
  39. Stromal cell-derived factor-1alpha associates with heparan sulfates through the first beta-strand of the chemokine.
    J Biol Chem. 1999 Aug 20;274(34):23916-25 PMID: 10446158
  40. Chemokines: a new classification system and their role in immunity.
    Immunity. 2000 Feb;12(2):121-7 PMID: 10714678
Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI9775
Email
promagnani@iol.it
Published
2001-01-00
Pages
53-63
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC198541
Subset
IM
External Links
PubMed source DOI: 10.1172/JCI9775 PMC Full Text View journal details
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