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
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.
Figures in this publication
Available from: Jaap van Buul
- "In line with this, binding of leukocytes through ICAM-1 induces a local increase in F-actin content at sites of adhesion . VCAM-1 is weakly expressed on resting endothelium but is highly up-regulated upon stimulation with inflammatory mediators  . 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.
BioMed Research International 03/2010; 2010:120328. DOI:10.1155/2010/120328 · 2.71 Impact Factor
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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.
Current Pharmaceutical Design 02/2005; 11(7):893-901. DOI:10.2174/1381612053381710 · 3.45 Impact Factor
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ABSTRACT: Bone marrow (BM) cells form differentiated adult lineages within nonhematopoietic tissues, with a heightened propensity with increasing regenerative pressure dictated by disease. We have previously shown that BM cells engraft into the gut and contribute substantially to the subepithelial intestinal myofibroblast population in the lamina propria. To investigate the reparative capacity of BM in inflammatory bowel disease (IBD), a well-established model of experimental colitis was used.
Lethally irradiated female mice were rescued by a BM transplant from male donors. Colitis was induced 6 weeks posttransplantation by injection of trinitrobenzene sulfonic acid (TNBS), and tissues were analyzed 1-14 days later. Donor-derived cells were detected by in situ hybridization using a Y chromosome-specific probe, and their phenotype was determined by immunohistochemistry.
TNBS-induced colitis was manifest as patchy lesions that increased in severity between days 1 and 8, and the mucosa gradually regenerated between days 8 and 14. The contribution of BM to intestinal myofibroblasts was significantly increased in regions of colitis compared with noninflamed regions. Furthermore, BM-derived endothelial cells, pericytes, and vascular smooth muscle cells were frequently interspersed throughout blood vessels, suggesting that these cells facilitate angiogenesis in tissue repair, substantiated by a significant increase in the incidence of BM-derived vascular smooth muscle cells in colitic compared with noninflamed regions. Blood vessels formed entirely from BM-derived cells were also seen, suggesting a role for BM in neovasculogenesis.
Our data show that BM contributes to multiple intestinal cell lineages in colitis, with an important function in tissue regeneration and vasculogenesis after injury.
Gastroenterology 07/2005; 128(7):1984-95. DOI:10.1053/j.gastro.2005.03.028 · 16.72 Impact Factor
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