Expression of VE-Cadherin in Peritubular Endothelial Cells during
Acute Rejection after Human Renal Transplantation
Ana Roussoulières,1,2Brigitte McGregor,3Lara Chalabreysse,4Catherine Cerutti,1Jeanne-Luce Garnier,5Pascale Boissonnat,2Olivier Bastien,2Jean-Yves Scoazec,3Françoise Thivolet-Bejui,4Laurent Sebbag,2and John L. McGregor1,6
Academic Editor: Abdelali Haoudi
Received29 Nov 2006
Accepted10 May 2007
Published26 Jul 2007
Abstract
Genes involved in acute rejection (AR) after organ transplantation remain to be
further elucidated. In a previous work we have demonstrated the under-expression of
VE-Cadherin by endothelial cells (EC) in AR following murine and human heart
transplantation. Serial sections from 15 human kidney Banff-graded transplant biopsies
were examined for the presence of VE-Cadherin and CD34 staining by
immunohistochemistry (no AR (n=5), AR grade IA (n=5), or AR grade IIA (n=5)). Quantification of peritubular EC staining were evaluated and results were
expressed by the percentage of stained cells per surface analysed. There was no difference in
CD34 staining between the 3 groups. VE-Cadherin expression was significantly reduced in AR
Grade IIA when compared to no AR (P=.01) and to AR grade IA (P=.02). This study demonstrates a reduced VE-Cadherin expression by EC in
AR after renal transplantation. The down-regulation of VE-Cadherin may strongly participate
in human AR.
References
M. L. Rose, “Endothelial cells as antigen-presenting cells: role in human transplant rejection,” Cellular and Molecular Life Sciences, vol. 54, no. 9, pp. 965–978, 1998.
A. S. Daar, S. V. Fuggle, J. W. Fabre, A. Ting, and P. J. Morris, “The detailed distribution of MHC class II antigens in normal human organs,” Transplantation, vol. 38, no. 3, pp. 293–298, 1984.
M. L. Rose, M. I. Coles, R. J. Griffin, A. Pomerance, and M. H. Yacoub, “Expression of class I and class II major histocompatibility antigens in normal and transplanted human heart,” Transplantation, vol. 41, no. 6, pp. 776–780, 1986.
C. Page, M. Rose, M. Yacoub, and R. Pigott, “Antigenic heterogeneity of vascular endothelium,” American Journal of Pathology, vol. 141, no. 3, pp. 673–683, 1992.
T. A. Springer, “Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm,” Cell, vol. 76, no. 2, pp. 301–314, 1994.
D. L. Simmons, C. Walker, C. Power, and R. Pigott, “Molecular cloning of CD31, a putative intercellular adhesion molecule closely related to carcinoembryonic antigen,” Journal of Experimental Medicine, vol. 171, no. 6, pp. 2147–2152, 1990.
M. G. Lampugnani, M. Resnati, E. Dejana, and P. C. Marchisio, “The role of integrins in the maintenance of endothelial monolayer integrity,” Journal of Cell Biology, vol. 112, no. 3, pp. 479–490, 1991.
R. L. Heimark, M. Degner, and S. M. Schwartz, “Identification of a -dependent cell-cell adhesion molecule in endothelial cells,” Journal of Cell Biology, vol. 110, no. 5, pp. 1745–1756, 1990.
S. Suzuki, K. Sano, and H. Tanihara, “Diversity of the cadherin family: evidence for eight new cadherins in nervous tissue,” Cell regulation, vol. 2, no. 4, pp. 261–270, 1991.
M. G. Lampugnani, M. Resnati, M. Raiteri et al., “A novel endothelial-specific membrane protein is a marker of cell-cell contacts,” Journal of Cell Biology, vol. 118, no. 6, pp. 1511–1522, 1992.
M. G. Lampugnani, M. Corada, L. Caveda et al., “The molecular organization of endothelial cell to cell junctions: differential association of plakoglobin, -catenin, and -catenin with vascular endothelial cadherin (VE-cadherin),” Journal of Cell Biology, vol. 129, no. 1, pp. 203–217, 1995.
R. Renkonen, J. P. Turunen, J. Rapola, and P. Hayry, “Characterization of high endothelial-like properties of peritubular capillary endothelium during acute renal allograft rejection,” American Journal of Pathology, vol. 137, no. 3, pp. 643–651, 1990.
A. Roussoulières, O. Raisky, L. Chalabreysse et al., “Identification and characterization of two genes (MIP-1, VE-cadherin) implicated in acute rejection in human heart transplantation—use of murine models in tandem with cDNA arrays,” Circulation, vol. 111, no. 20, pp. 2636–2644, 2005.
L. C. Racusen, K. Solez, R. B. Colvin et al., “The Banff 97 working classification of renal allograft pathology,” Kidney International, vol. 55, no. 2, pp. 713–723, 1999.
T. A. Springer, “Traffic signals on endothelium for lymphocyte recirculation and leukocyte emigration,” Annual Review of Physiology, vol. 57, pp. 827–872, 1995.
S. D. Trocha, C. G. Kevil, M. C. Mancini, and J. S. Alexander, “Organ preservation solutions increase endothelial permeability and promote loss of junctional proteins,” Annals of Surgery, vol. 230, no. 1, pp. 105–113, 1999.
M. Corada, F. Liao, M. Lindgren et al., “Monoclonal antibodies directed to different regions of vascular endothelial cadherin extracellular domain affect adhesion and clustering of the protein and modulate endothelial permeability,” Blood, vol. 97, no. 6, pp. 1679–1684, 2001.
C. Bianchi, E. G. Araujo, K. Sato, and F. W. Sellke, “Biochemical and structural evidence for pig myocardium adherens junction disruption by cardiopulmonary bypass,” Circulation, vol. 104, supplement 1, pp. I319–I324, 2001.
S. K. Shaw, P. S. Bamba, B. N. Perkins, and F. W. Luscinskas, “Real-time imaging of vascular endothelial-cadherin during leukocyte transmigration across endothelium,” Journal of Immunology, vol. 167, no. 4, pp. 2323–2330, 2001.
A. Del Maschio, A. Zanetti, M. Corada et al., “Polymorphonuclear leukocyte adhesion triggers the disorganization of endothelial cell-to-cell adherens junctions,” Journal of Cell Biology, vol. 135, no. 2, pp. 497–510, 1996.
E. C. Butcher, “Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity,” Cell, vol. 67, no. 6, pp. 1033–1036, 1991.
T. A. Sutton, H. E. Mang, S. B. Campos, R. M. Sandoval, M. C. Yoder, and B. A. Molitoris, “Injury of the renal microvascular endothelium alters barrier function after ischemia,” American Journal of Physiology, vol. 285, no. 2, pp. F191–F198, 2003.
C. Cerini, L. Dou, F. Anfosso et al., “P-cresol, a uremic retention solute, alters the endothelial barrier function in vitro,” Thrombosis and Haemostasis, vol. 92, no. 1, pp. 140–150, 2004.