ICAM-3 Activation Modulates Cell-Cell Contacts of Human Bone Marrow Endothelial Cells

Department of Experimental Immunohematology, Sanquin Research at CLB and the Landsteiner Laboratorium, University of Amsterdam, Amsterdam, The Netherlands.
Journal of Vascular Research (Impact Factor: 2.9). 02/2004; 41(1):28-37. DOI: 10.1159/000076126
Source: PubMed


The Ig-like cell adhesion molecule ICAM-3 is mainly expressed on human leukocytes and is involved in cell-cell interactions. Its expression on endothelium is observed during disorders such as Crohn's disease and in solid tumors. We found low but detectable expression of ICAM-3 on VE-cadherin-expressing cells from primary human bone marrow aspirates, i.e. endothelial cells, and on primary human endothelial cells from cord blood. Also, immortalized human umbilical cord endothelial cells and human bone marrow endothelial cells showed ICAM-3 expression. However, its function on human endothelium is not known. Surprisingly, activation of endothelial ICAM-3 by crosslinking with specific antibodies resulted in a drop in the electrical resistance of bone marrow endothelial monolayers. In line with this, immunocytochemical analysis showed a loss of endothelial cell-cell contacts after ICAM-3 crosslinking in HBMEC. Detailed biochemical analysis showed an association of moesin and in a later stage ezrin with ICAM-3 upon crosslinking in HBMEC. Moreover, ICAM-3 crosslinking induced the production of reactive oxygen species (ROS), which are known to be involved in the control of endothelial cell-cell contacts. In conclusion, we showed that ICAM-3 is expressed on human bone marrow endothelial cells and controls endothelial integrity via ROS-dependent signaling.

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    • "Previous research demonstrates that ezrin contributes to cytoskeletal processes underlying many cellular functions including cell division, adhesion and migration (Brambilla and Fais, 2009;Federici et al., 2009;Ren et al., 2009). Ezrin may participate in cell adhesion events by interacting with cell-surface adhesion molecules (Granés et al., 2000;Lozupone et al., 2004;van Buul et al., 2004;Yang et al., 2009). In its activated form, ezrin binds to membrane proteins such as CD43, CD44, CD95, ICAM 1-3, syndecan-2 and E-Cadherin by its N-terminal domain (Granés et al., 2000;Morrison et al., 2001;Lozupone et al., 2004;Yang et al., 2009). "
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    ABSTRACT: Ezrin is a member of the ezrin–radixin–moesin (ERM) family of membrane–cytoskeletal linkage proteins. It is important for maintenance of cell shape, adhesion, migration and division. The overexpression of ezrin in some tumours is associated with increased cell migration that is mediated by the Rho/ROCK family of small GTPases. To investigate the role of ezrin in the migration of ectopic endometrial cells in endometriosis, we conducted real-time quantitative RT–PCR analysis of the eutopic and ectopic endometrium from women with endometriosis compared with those without the disease. RNAi, wound healing assays and western blot analysis of endometriotic cells were also included in this research. We found significantly higher levels of mRNA expression of ezrin (0.42 versus 0.27, P < 0.05), RhoA (0.99 versus 0.74, P < 0.05), RhoC (0.79 versus 0.43, P < 0.005) and ROCK1 (0.68 versus 0.38, P < 0.005) in the ectopic endometrial cells compared with the eutopic endometrial cells in endometriosis. Blocking ezrin with small-interfering RNA reduced the migration of ectopic endometrial cells with decreased expression of RhoA (42.68%), RhoC (58.42%) and ROCK1 (59.88%). Our results indicate that the over-expression of ezrin in endometriosis may play a significant role in the migration of endometrial cells of endometriosis, and the RhoC/Rock pathway may provide a promising treatment target.
    Preview · Article · Apr 2012 · Molecular Human Reproduction
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    • "In line with this, binding of leukocytes through ICAM-1 induces a local increase in F-actin content at sites of adhesion [6]. VCAM-1 is weakly expressed on resting endothelium but is highly up-regulated upon stimulation with inflammatory mediators [2] [3]. Leukocytes adhere through the integrin VLA-4 to VCAM-1 on the endothelium. "
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    ABSTRACT: In the initial stages of transendothelial migration, leukocytes use the endothelial integrin ligands ICAM-1 and VCAM-1 for strong adhesion. Upon adhesion of the leukocyte to endothelial ICAM-1, ICAM-1 is clustered and recruited to the adhered leukocyte, promoting strong adhesion. In this study, we provide evidence for the colocalization of VCAM-1 at sites of ICAM-1 clustering. Anti-ICAM-1 antibody-coated beads were used to selectively cluster and recruit ICAM-1 on primary human endothelial cells. In time, co-localization of ICAM-1 and VCAM-1 around the adherent beads was observed. Biochemical pull-down assays showed that ICAM-1 clustering induced its association to VCAM-1, suggesting a physical link between these two adhesion molecules. The association was partly dependent on lipid rafts as well as on F-actin and promoted adhesion. These data show that VCAM-1 can be recruited, in an integrin-independent fashion, to clustered ICAM-1 which may serve to promote ICAM-1-mediated leukocyte adhesion.
    Full-text · Article · Mar 2010 · BioMed Research International
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    ABSTRACT: Integrins are a family of heterodimeric transmembrane glycoproteins that mediate cell-cell and cell-matrix interactions. They participate in inflammatory reactions mainly by regulation of leukocyte migration, activation and survival. Elevated expression of the cell adhesion molecules, such as VCAM, ICAM and MAdCAM on the lumenal surface of vascular endothelial cells is a critical early event in organ inflammatory processes - including the lung. Adhesive interactions with their counter-receptors on leukocytes, selectins and integrins, result in migration of the leukocytes to the inflammed tissues. Integrins also participate in physiological and pathological reorganization of the lung structure during e.g. pneumonia healing, airway remodeling, angiogenesis, emphysema and pulmonary fibrosis. Agents that could inhibit the function of one or more of these integrins could provide a novel therapeutic strategy targeted to inhibit inflammatory and immune phenomena in the lung.
    No preview · Article · Feb 2005 · Current Pharmaceutical Design
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