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VCAM-1-mediated Rac signaling controls endothelial cell-cell contacts and leukocyte transmigration

van Wetering, Sandra, van den Berk, Nadia, van Buul, Jaap D., Mul, Frederik P. J., Lommerse, Ingrid, Mous, Rogier, Klooster, Jean-Paul ten, Zwaginga, Jaap-Jan, Hordijk, Peter L.·2003·American Journal of Physiology-Cell Physiology
DOI 10.1152/ajpcell.00048.2003
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Abstract

Leukocyte adhesion is mediated totally and transendothelial migration partially by heterotypic interactions between the β 1- and β 2-integrins on the leukocytes and their ligands, Ig-like cell adhesion molecules (Ig-CAM), VCAM-1, and ICAM-1, on the endothelium. Both integrins and Ig-CAMs are known to have signaling capacities. In this study we analyzed the role of VCAM-1-mediated signaling in the control of endothelial cell-cell adhesion and leukocyte transendothelial migration. Antibody-mediated cross-linking of VCAM-1 on IL-1β-activated primary human umbilical vein endothelial cells (pHUVEC) induced actin stress fiber formation, contractility, and intercellular gaps. The effects induced by VCAM-1 cross-linking were inhibited by C3 toxin, indicating that the small GTPase p21Rho is involved. In addition, the effects of VCAM-1 were accompanied by activation of Rac, which we recently showed induce intercellular gaps in pHUVEC in a Rho-dependent fashion. With the use of a cell-permeable peptide inhibitor, it was shown that Rac signaling is required for VCAM-1-mediated loss of cell-cell adhesion. Furthermore, VCAM-1-mediated signaling toward cell-cell junctions was accompanied by, and dependent on, Rac-mediated production of reactive oxygen species and activation of p38 MAPK. In addition, it was found that inhibition of Rac-mediated signaling blocks transendothelial migration of monocytic U937 cells. Together, these data indicate that VCAM-1-induced, Rac-dependent signaling plays a key role in the modulation of vascular-endothelial cadherin-mediated endothelial cell-cell adhesion and leukocyte extravasation.

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Research works printed but not linked: 63

  1. Adamson P, Etienne S, Couraud PO, Calder V, and Green-wood J. Lymphocyte migration through brain endothelial cell monolayers involves signaling through endothelial ICAM-1 via a rho-dependent pathway. J Immunol 162: 2964–2973, 1999. · DOI
  2. Alon R, Kassner PD, Carr MW, Finger EB, Hemler ME, and Springer TA. The integrin VLA-4 supports tethering and rolling in flow on VCAM-1. J Cell Biol 128: 1243–1253, 1995. · DOI
  3. Barreiro O, Yanez-Mo M, Serrador JM, Montoya MC, Vicente-Manzanares M, Tejedor R, Furthmayr H, and Sanchez-Madrid F. Dynamic interaction of VCAM-1 and ICAM-1 with moesin and ezrin in a novel endothelial docking structure for adherent leukocytes. J Cell Biol 157: 1233–1245, 2002. · DOI
  4. Bazzoni G and Dejana E. Pores in the sieve and channels in the wall: control of paracellular permeability by junctional proteins in endothelial cells. Microcirculation 8: 143–152, 2001. · DOI
  5. Blanchetot C, Tertoolen LG, and den Hertog J. Regulation of receptor protein-tyrosine phosphatase alpha by oxidative stress. EMBO J 21: 493–503, 2002. · DOI
  6. Braga VM, Machesky LM, Hall A, and Hotchin NA. The small GTPases Rho and Rac are required for the establishment of cadherin-dependent cell-cell contacts. J Cell Biol 137: 1421–1431, 1997. · DOI
  7. Brinkman HJ, Mertens K, Holthuis J, Zwart-Huinink LA, Grijm K, and van Mourik JA. The activation of human blood coagulation factor X on the surface of endothelial cells: a comparison with various vascular cells, platelets and monocytes. Br J Haematol 87: 332–342, 1994. · DOI
  8. Bunting M, Harris ES, McIntyre TM, Prescott SM, and Zimmerman GA. Leukocyte adhesion deficiency syndromes: adhesion and tethering defects involving beta 2 integrins and selectin ligands. Curr Opin Hematol 9: 30–35, 2002. · DOI
  9. Chuluyan HE and Issekutz AC. VLA-4 integrin can mediate CD11/CD18-independent transendothelial migration of human monocytes. J Clin Invest 92: 2768–2777, 1993. · DOI
  10. Cinamon G, Grabovsky V, Winter E, Franitza S, Feigelson S, Shamri R, Dwir O, and Alon R. Novel chemokine functions in lymphocyte migration through vascular endothelium under shear flow. J Leukoc Biol 69: 860–866, 2001. · DOI
  11. Cinamon G, Shinder V, and Alon R. Shear forces promote lymphocyte migration across vascular endothelium bearing apical chemokines. Nat Immun 2: 515–522, 2001. · DOI
  12. Colavitti R, Pani G, Bedogni B, Anzevino R, Borrello S, Waltenberger J, and Galeotti T. Reactive oxygen species as downstream mediators of angiogenic signaling by vascular endothelial growth factor receptor-2/KDR. J Biol Chem 277: 3101–3108, 2002. · DOI
  13. Cybulsky MI, Iiyama K, Li H, Zhu S, Chen M, Iiyama M, Davis V, Gutierrez-Ramos JC, Connelly PW, and Milstone DS. A major role for VCAM-1, but not ICAM-1, in early atherosclerosis. J Clin Invest 107: 1255–1262, 2001. · DOI
  14. Dejana E, Bazzoni G, and Lampugnani MG. Vascular endothelial (VE)-cadherin: only an intercellular glue? Exp Cell Res 252: 13–19, 1999. · DOI
  15. Dejana E, Corada M, and Lampugnani MG. Endothelial cell-to-cell junctions. FASEB J 9: 910–918, 1995. · DOI
  16. Dejana E, Spagnuolo R, and Bazzoni G. Interendothelial junctions and their role in the control of angiogenesis, vascular permeability and leukocyte transmigration. Thromb Haemost 86: 308–315, 2001. · DOI
  17. DeLisser HM, Newman PJ, and Albelda SM. Molecular and functional aspects of PECAM-1/CD31. Immunol Today 15: 490–495, 1994. · DOI
  18. Durieu-Trautmann O, Chaverot N, Cazaubon S, Strosberg AD, and Couraud PO. Intercellular adhesion molecule 1 activation induces tyrosine phosphorylation of the cytoskeleton-associated protein cortactin in brain microvessel endothelial cells. J Biol Chem 269: 12536–12540, 1994. · DOI
  19. Etienne S, Adamson P, Greenwood J, Strosberg AD, Cazaubon S, and Couraud PO. ICAM-1 signaling pathways associated with Rho activation in microvascular brain endothelial cells. J Immunol 161: 5755–5761, 1998. · DOI
  20. Etienne-Manneville S, Manneville JB, Adamson P, Wilbourn B, Greenwood J, and Couraud PO. ICAM-1-coupled cytoskeletal rearrangements and transendothelial lymphocyte migration involve intracellular calcium signaling in brain endothelial cell lines. J Immunol 165: 3375–3383, 2000. · DOI
  21. Ferrero E, Zocchi MR, Magni E, Panzeri MC, Curnis F, Rugarli C, Ferrero ME, and Corti A. Roles of tumor necrosis factor p55 and p75 receptors in TNF-alpha-induced vascular permeability. Am J Physiol Cell Physiol 281: C1173–C1199, 2001. · DOI
  22. Garcia JG, Verin AD, Herenyiova M, and English D. Adherent neutrophils activate endothelial myosin light chain kinase: role in transendothelial migration. J Appl Physiol 84: 1817–1821, 1998. · DOI
  23. Gotsch U, Borges E, Bosse R, Boggemeyer E, Simon M, Mossmann H, and Vestweber D. VE-cadherin antibody accelerates neutrophil recruitment in vivo. J Cell Sci 110: 583–588, 1997. · DOI
  24. Hakkert BC, Rentenaar JM, and van Mourik JA. Monocytes enhance the bidirectional release of type I plasminogen activator inhibitor by endothelial cells. Blood 76: 2272–2278, 1990. · DOI
  25. Hixenbaugh EA, Goeckeler ZM, Papaiya NN, Wysolmerski RB, Silverstein SC, and Huang AJ. Stimulated neutrophils induce myosin light chain phosphorylation and isometric tension in endothelial cells. Am J Physiol Heart Circ Physiol 273: H981–H988, 1997. · DOI
  26. Hogg N and Berlin C. Structure and function of adhesion receptors in leukocyte trafficking. Immunol Today 16: 327–330, 1995. · DOI
  27. Hordijk PL, Anthony E, Mul FP, Rientsma R, Oomen LC, and Roos D. Vascular-endothelial-cadherin modulates endothelial monolayer permeability. J Cell Sci 112: 1915–1923, 1999. · DOI
  28. Hordijk PL, ten Klooster JP, van der Kammen RA, Michiels F, Oomen LC, and Collard JG. Inhibition of invasion of epithelial cells by Tiam1-Rac signaling. Science 278: 1464–1466, 1997. · DOI
  29. Huang AJ, Manning JE, Bandak TM, Ratau MC, Hanser KR, and Silverstein SC. Endothelial cell cytosolic free calcium regulates neutrophil migration across monolayers of endothelial cells. J Cell Biol 120: 1371–1380, 1993. · DOI
  30. Huot J, Houle F, Marceau F, and Landry J. Oxidative stress-induced actin reorganization mediated by the p38 mitogen-activated protein kinase/heat shock protein 27 pathway in vascular endothelial cells. Circ Res 80: 383–392, 1997. · DOI
  31. Katsumi A, Milanini J, Kiosses WB, del Pozo MA, Kaunas R, Chien S, Hahn KM, and Schwartz MA. Effects of cell tension on the small GTPase Rac. J Cell Biol 158: 153–164, 2002. · DOI
  32. Kayyali US, Pennella CM, Trujillo C, Villa O, Gaestel M, and Hassoun PM. Cytoskeletal changes in hypoxic pulmonary endothelial cells are dependent on MAPK-associated protein kinase MK2. J Biol Chem 277: 42596–42602, 2002. · DOI
  33. Kiemer AK, Weber NC, Furst R, Bildner N, Kulhanek-Heinze S, and Vollmar AM. Inhibition of p38 MAPK activation via induction of MKP-1: atrial natriuretic peptide reduces TNF-alpha-induced actin polymerization and endothelial permeability. Circ Res 90: 874–881, 2002. · DOI
  34. Lambeth JD. Nox/Duox family of nicotinamide adenine dinucleotide (phosphate) oxidases. Curr Opin Hematol 9: 11–17, 2002. · DOI
  35. Lawson C, Ainsworth M, Yacoub M, and Rose M. Ligation of ICAM-1 on endothelial cells leads to expression of VCAM-1 via a nuclear factor-kappaB-independent mechanism. J Immunol 162: 2990–2996, 1999. · DOI
  36. Li JM and Shah AM. Intracellular localization and preassembly of the NADPH oxidase complex in cultured endothelial cells. J Biol Chem 277: 19952–19960, 2002. · DOI
  37. Lorenzon P, Vecile E, Nardon E, Ferrero E, Harlan JM, Tedesco F, and Dobrina A. Endothelial cell E- and P-selectin and vascular cell adhesion molecule-1 function as signaling receptors. J Cell Biol 142: 1381–1391, 1998. · DOI
  38. Lum H and Roebuck KA. Oxidant stress and endothelial cell dysfunction. Am J Physiol Cell Physiol 280: C719–C741, 2001. · DOI
  39. Matheny HE, Deem TL, and Cook-Mills JM. Lymphocyte migration through monolayers of endothelial cell lines involves VCAM-1 signaling via endothelial cell NADPH oxidase. J Immunol 164: 6550–6559, 2000. · DOI
  40. Nagahara H, Vocero-Akbani AM, Snyder EL, Ho A, Latham DG, Lissy NA, Becker-Hapak M, Ezhevsky SA, and Dowdy SF. Transduction of full-length TAT fusion proteins into mammalian cells: TAT-p27Kip1 induces cell migration. Nat Med 4: 1449–1452, 1998. · DOI
  41. Ng CK, Deshpande SS, Irani K, and Alevriadou BR. Adhesion of flowing monocytes to hypoxia-reoxygenation-exposed endothelial cells: role of Rac1, ROS, and VCAM-1. Am J Physiol Cell Physiol 283: C93–C102, 2002. · DOI
  42. Nwariaku FE, Chang J, Zhu X, Liu Z, Duffy SL, Halaihel NH, Terada L, and Turnage RH. The role of p38 map kinase in tumor necrosis factor-induced redistribution of vascular endothelial cadherin and increased endothelial permeability. Shock 18: 82–85, 2002. · DOI
  43. Ricard I, Payet MD, and Dupuis G. Clustering the adhesion molecules VLA-4 (CD49d/CD29) in Jurkat T cells or VCAM-1 (CD106) in endothelial (ECV 304) cells activates the phosphoinositide pathway and triggers Ca2+ mobilization. Eur J Immunol 27: 1530–1538, 1997. · DOI
  44. Rousseau S, Houle F, Landry J, and Huot J. p38 MAP kinase activation by vascular endothelial growth factor mediates actin reorganization and cell migration in human endothelial cells. Oncogene 15: 2169–2177, 1997. · DOI
  45. Saito H, Minamiya Y, Kitamura M, Saito S, Enomoto K, Terada K, and Ogawa J. Endothelial myosin light chain kinase regulates neutrophil migration across human umbilical vein endothelial cell monolayer. J Immunol 161: 1533–1540, 1998. · DOI
  46. Sanchez-Mateos P, Cabanas C, and Sanchez-Madrid F. Regulation of integrin function. Semin Cancer Biol 7: 99–109, 1996. · DOI
  47. Sander EE, van Delft S, ten Klooster JP, Reid T, van der Kammen RA, Michiels F, and Collard JG. Matrix-dependent Tiam1/Rac signaling in epithelial cells promotes either cell-cell adhesion or cell migration and is regulated by phosphatidylinositol 3-kinase. J Cell Biol 143: 1385–1398, 1998. · DOI
  48. Sans E, Delachanal E, and Duperray A. Analysis of the roles of ICAM-1 in neutrophil transmigration using a reconstituted mammalian cell expression model: implication of ICAM-1 cytoplasmic domain and Rho-dependent signaling pathway. J Immunol 166: 544–551, 2001. · DOI
  49. Shaw SK, Bamba PS, Perkins BN, and Luscinskas FW. Real-time imaging of vascular endothelial-cadherin during leukocyte transmigration across endothelium. J Immunol 167: 2323–2330, 2001. · DOI
  50. Sigal A, Bleijs DA, Grabovsky V, van Vliet SJ, Dwir O, Figdor CG, van Kooyk Y, and Alon R. The LFA-1 integrin supports rolling adhesions on ICAM-1 under physiological shear flow in a permissive cellular environment. J Immunol 165: 442–452, 2000. · DOI
  51. Smith CW. Endothelial adhesion molecules and their role in inflammation. Can J Physiol Pharmacol 71: 76–87, 1993. · DOI
  52. Springer TA. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 76: 301–314, 1994. · DOI
  53. Takaishi K, Sasaki T, Kotani H, Nishioka H, and Takai Y. Regulation of cell-cell adhesion by rac and rho small G proteins in MDCK cells. J Cell Biol 139: 1047–1059, 1997. · DOI
  54. Ukropec JA, Hollinger MK, Salva SM, and Woolkalis MJ. SHP2 association with VE-cadherin complexes in human endothelial cells is regulated by thrombin. J Biol Chem 275: 5983–5986, 2000. · DOI
  55. Van Buul JD, Voermans C, van den Berg V, Anthony EC, Mul FP, van Wetering S, van der Schoot CE, and Hordijk PL. Migration of human hematopoietic progenitor cells across bone marrow endothelium is regulated by vascular endothelial cadherin. J Immunol 168: 588–596, 2002. · DOI
  56. Van Wetering S, van Buul JD, Quik S, Mul FP, Anthony EC, ten Klooster JP, Collard JG, and Hordijk PL. Reactive oxygen species mediate Rac-induced loss of cell-cell adhesion in primary human endothelial cells. J Cell Sci 115: 1837–1846, 2002. · DOI
  57. Vastrik I, Eickholt BJ, Walsh FS, Ridley A, and Doherty P. Sema3A-induced growth-cone collapse is mediated by Rac1 amino acids 17–32. Curr Biol 9: 991–998, 1999. · DOI
  58. Volberg T, Zick Y, Dror R, Sabanay I, Gilon C, Levitzki A, and Geiger B. The effect of tyrosine-specific protein phosphorylation on the assembly of adherens-type junctions. EMBO J 11: 1733–1742, 1992. · DOI
  59. Vouret-Craviari V, Grall D, Flatau G, Pouyssegur J, Boquet P, and Van Obberghen-Schilling E. Effects of cytotoxic necrotizing factor 1 and lethal toxin on actin cytoskeleton and VE-cadherin localization in human endothelial cell monolayers. Infect Immun 67: 3002–3008, 1999. · DOI
  60. Wegener J, Keese CR, and Giaever I. Electric cell-substrate impedance sensing (ECIS) as a noninvasive means to monitor the kinetics of cell spreading to artificial surfaces. Exp Cell Res 259: 158–166, 2000. · DOI
  61. Wojciak-Stothard B, Entwistle A, Garg R, and Ridley AJ. Regulation of TNF-alpha-induced reorganization of the actin cytoskeleton and cell-cell junctions by Rho, Rac, and Cdc42 in human endothelial cells. J Cell Physiol 176: 150–165, 1998. · DOI
  62. Worthylake RA and Burridge K. Leukocyte transendothelial migration: orchestrating the underlying molecular machinery. Curr Opin Cell Biol 13: 569–577, 2001. · DOI
  63. Yonemura S, Hirao M, Doi Y, Takahashi N, Kondo T, and Tsukita S. Ezrin/radixin/moesin (ERM) proteins bind to a positively charged amino acid cluster in the juxta-membrane cytoplasmic domain of CD44, CD43, and ICAM-2. J Cell Biol 140: 885–895, 1998. · DOI

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Metadata

Authors
van Wetering, S., van den Berk, N., van Buul, J. D., Mul, F. P. J., Lommerse, I., Mous, R., Klooster, J.-P. T., Zwaginga, J.-J., & Hordijk, P. L.
Venue
American Journal of Physiology-Cell Physiology
Publisher
American Physiological Society
Published
2003-08
Volume
285
Issue
2
Pages
C343-C352
ISSN
  • 0363-6143
  • 1522-1563
DOI
10.1152/ajpcell.00048.2003
Cited by
185
References
0
Language
en

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CoChat. (2026). Citation check: VCAM-1-mediated Rac signaling controls endothelial cell-cell contacts and leukocyte transmigration. https://app.cochat.ai/papers/10.1152/ajpcell.00048.2003
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van Wetering, S., van den Berk, N., van Buul, J. D., Mul, F. P. J., Lommerse, I., Mous, R., Klooster, J.-P. T., Zwaginga, J.-J., & Hordijk, P. L. (2003). VCAM-1-mediated Rac signaling controls endothelial cell-cell contacts and leukocyte transmigration. American Journal of Physiology-Cell Physiology. https://doi.org/10.1152/ajpcell.00048.2003