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.

Keywords:
ICAM-3, Endothelium, Reactive oxygen species, Resistance, Bone marrow
1.
Johnson-Leger C, Aurrand-Lions M, Imhof B: The parting of the endothelium: Miracle, or simply a junctional affair? J Cell Sci 2000;113:921–933.
2.
Geijtenbeek TB, Krooshoop DJ, Bleijs DA, van Vliet SJ, van Duijnhoven GC, Grabovsky V, Alon R, Figdor CG, van Kooyk Y: DC-SIGN-ICAM-2 interaction mediates dendritic cell trafficking. Nat Immunol 2000;1:353–357.
3.
Muller WA, Weigl SA, Deng X, Phillips DM: PECAM-1 is required for transendothelial migration of leukocytes. J Exp Med 1993;178:449–460.
4.
Campanero MR, del Pozo MA, Arroyo AG, Sanchez-Mateos P, Hernandez-Caselles T, Craig A, Pulido R, Sanchez-Madrid F: ICAM-3 interacts with LFA-1 and regulates the LFA-1/ICAM-1 cell adhesion pathway. J Cell Biol 1993;123:1007–1016.
5.
Juan M, Vinas O, Pino-Otin MR, Places L, Martinez-Caceres E, Barcelo JJ, Miralles A, Vilella R, de la Fuente MA, Vives J, et al: CD50 (intercellular adhesion molecule 3) stimulation induces calcium mobilization and tyrosine phosphorylation through p59fyn and p56lck in Jurkat T cell line. J Exp Med 1994;179:1747–1756.
6.
Fawcett J, Holness CL, Needham LA, Turley H, Gatter KC, Mason DY, Simmons DL: Molecular cloning of ICAM-3, a third ligand for LFA-1, constitutively expressed on resting leukocytes. Nature 1992;360:481–484.
7.
Bretscher A, Chambers D, Nguyen R, Reczek D: ERM-Merlin and EBP50 protein families in plasma membrane organization and function. Annu Rev Cell Dev Biol 2000;16:113–143.
8.
Alonso-Lebrero JL, Serrador JM, Dominguez-Jimenez C, Barreiro O, Luque A, del Pozo MA, Snapp K, Kansas G, Schwartz-Albiez R, Furthmayr H, Lozano F, Sanchez-Madrid F: Polarization and interaction of adhesion molecules P-selectin glycoprotein ligand 1 and intercellular adhesion molecule 3 with moesin and ezrin in myeloid cells. Blood 2000;95:2413–2419.
9.
Serrador JM, Alonso-Lebrero JL, del Pozo MA, Furthmayr H, Schwartz-Albiez R, Calvo J, Lozano F, Sanchez-Madrid F: Moesin interacts with the cytoplasmic region of intercellular adhesion molecule-3 and is redistributed to the uropod of T lymphocytes during cell polarization. J Cell Biol 1997;138:1409–1423.
10.
Verkarre V, Patey-Mariaud de Serre N, Vazeux R, Teillac-Hamel D, Chretien-Marquet B, Le Bihan C, Leborgne M, Fraitag S, Brousse N: ICAM-3 and E-selectin endothelial cell expression differentiate two phases of angiogenesis in infantile hemangiomas. J Cutan Pathol 1999;26:17–24.
11.
Fox SB, Turner GD, Gatter KC, Harris AL: The increased expression of adhesion molecules ICAM-3, E- and P-selectins on breast cancer endothelium. J Pathol 1995;177:369–376.
12.
Vainer B, Nielsen OH: Changed colonic profile of P-selectin, platelet-endothelial cell adhesion molecule-1 (PECAM-1), intercellular adhesion molecule-1 (ICAM-1), ICAM-2, and ICAM-1 in inflammatory bowel disease. Clin Exp Immunol 2000;121:242–247.
13.
Patey N, Vazeux R, Canioni D, Potter T, Gallatin WM, Brousse N: Intercellular adhesion molecule-3 on endothelial cells. Expression in tumors but not in inflammatory responses. Am J Pathol 1996;148:465–472.
14.
Neelamegham S, Taylor AD, Shankaran H, Smith CW, Simon SI: Shear and time-dependent changes in Mac-1, LFA-1, and ICAM-3 binding regulate neutrophil homotypic adhesion. J Immunol 2000;164:3798–3805.
15.
Rood PM, Calafat J, von dem Borne AEGK, Gerritsen WR, van der Schoot CE: Immortalization of human bone-marrow endothelial cells: Characterization of new cell lines. Eur J Clin Invest 2000;30:473–478.
16.
Hordijk PL, Anthony E, Mul FP, Rientsma R, Oomen LC, Roos D: Vascular-endothelial-cadherin modulates endothelial monolayer permeability. J Cell Sci 1999;112:1915–1923.
17.
Van Buul JD, Voermans C, Van den Berg V, Anthony E, Mul F, Van Wetering S, Van der Schoot CE, Hordijk PL: Migration of human hematopoietic progenitor cells across bone marrow endothelium is regulated by vascular endothelial cadherin. J Immunol 2002;168:588–596.
18.
Lorenzon P, Vecile E, Nardon E, Ferrero E, Harlan JM, Tedesco F, Dobrina A: Endothelial cell E- and P-selectin and vascular cell adhesion molecule-1 function as signaling receptors. J Cell Biol 1998;142:1381–1391.
19.
Matheny HE, Deem TL, Cook-Mills JM: Lymphocyte migration through monolayers of endothelial cell lines involves VCAM-1 signaling via endothelial cell NADPH oxidase. J Immunol 2000;164:6550–6559.
20.
Etienne-Manneville S, Manneville J-B, Adamson P, Wilbourn B, Greenwood J, Couraud P-O: ICAM-1-coupled cytoskeletal rearrangements and transendothelial lymphocyte migration involve intracellular calcium signaling in brain endothelial cell lines. J Immunol 2000;165:3375–3383.
21.
Carmeliet P, Collen D: Molecular basis of angiogenesis. Role of VEGF and VE-cadherin. Ann NY Acad Sci 2000;902:249–262.
22.
Etienne-Manneville S, Hall A: RhoGTPases in cell biology. Nature 2002;420:629–635.
23.
Shaw RJ, Henry M, Solomon F, Jacks T: RhoA-dependent phosphorylation and relocalization of ERM proteins into apical membrane/actin protrusions in fibroblasts. Mol Biol Cell 1998;9:403–419.
24.
Pujuguet P, Del Maestro L, Gautreau A, Louvard D, Arpin M: Ezrin regulates E-cadherin-dependent adherens junction assembly through Rac1 activation. Mol Biol Cell 2003;14:2181–2191.
25.
Wang Q, Doerschuk CM: Neutrophil-induced changes in the biomechanical properties of endothelial cells: Roles of ICAM-1 and reactive oxygen species. J Immunol 2000;164:6487–6494.
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2004
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