The junctional adhesion molecule 3 (JAM-3) on human platelets is a counterreceptor for the leukocyte integrin Mac-1
Sentot Santoso, Ulrich J H Sachs, Hartmut Kroll, Monica Linder, Andreas Ruf, Klaus T Preissner, Triantafyllos Chavakis, Sentot Santoso, Ulrich J H Sachs, Hartmut Kroll, Monica Linder, Andreas Ruf, Klaus T Preissner, Triantafyllos Chavakis
Abstract
The recently described junctional adhesion molecules (JAMs) in man and mice are involved in homotypic and heterotypic intercellular interactions. Here, a third member of this family, human JAM-3, was identified and described as a novel counterreceptor on platelets for the leukocyte beta2-integrin Mac-1 (alphaMbeta2, CD11b/CD18). With the help of two monoclonal antibodies, Gi11 and Gi13, against a 43-kD surface glycoprotein on human platelets, a full-length cDNA encoding JAM-3 was identified. JAM-3 is a type I transmembrane glycoprotein containing two Ig-like domains. Although JAM-3 did not undergo homophilic interactions, myelo-monocytic cells adhered to immobilized JAM-3 or to JAM-3-transfected cells. This heterophilic interaction was specifically attributed to a direct interaction of JAM-3 with the beta2-integrin Mac-1 and to a lower extent with p150.95 (alphaXbeta2, CD11c/CD18) but not with LFA-1 (alphaLbeta2, CD11a/CD18) or with beta1-integrins. These results were corroborated by analysis of K562 erythroleukemic cells transfected with different heterodimeric beta2-integrins and by using purified proteins. Moreover, purified JAM-3 or antibodies against JAM-3 blocked the platelet-neutrophil interaction, indicating that platelet JAM-3 serves as a counterreceptor for Mac-1 mediating leukocyte-platelet interactions. JAM-3 thereby provides a novel molecular target for antagonizing interactions between vascular cells that promote inflammatory vascular pathologies such as in atherothrombosis.
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References
- Springer, T.A. 1994. Traffic signals for lymphocyte recirculation and leukocyte emigration: a multistep paradigm. Cell. 76:301–314.
- Smith, C.W., S.D. Marlin, R. Rothlein, C. Toman, and D.C. Anderson. 1989. Cooperative interactions of LFA-1 and Mac-1 with intercellular adhesion molecule-1 in facilitating adherence and transendothelial migration of human neutrophils in vitro. J. Clin. Invest. 83:2008–2017.
- Languino, L.R., A. Duperray, K.J. Joganic, M. Fornaro, G.B. Thornton, and D.C. Altieri. 1995. Regulation of leukocyte-endothelial interactions and leukocyte transendothelial migration by intercellular adhesion molecule 1-fibrinogen recognition. Proc. Natl. Acad. Sci. USA. 92:7734–7738.
- Marcus, A.J. 1994. Thrombosis and inflammation as multicellular processes: significance of cell-cell interactions. Semin. Hematol. 31:261–269.
- Rinder, C.S., J.L. Bonan, H.M. Rinder, J. Matthew, R. Hines, and B.R. Smith. 1992. Cardiopulmonary bypass induces leukocyte-platelet adhesion. Blood. 79:1201–1205.
- Ross, R. 1999. Atherosclerosis-an inflammatory disease. N. Engl. J. Med. 340:115–126.
- McEver, R.P. 2001. Adhesive interactions of leukocytes, platelets and the vessel wall during hemostasis and inflammation. Thromb. Haemost. 86:746–756.
- Simon, D.I., C.P. Chen, H. Xu, C.Q. Li, J.F. Dong, L.V. McIntire, C.M. Ballantyne, L. Zhang, M.I. Furman, M.C. Berndt, and J.A. Lopez. 2000. Platelet glycoprotein Ibα is a counterreceptor for the leukocyte integrin Mac-1 (CD11b/CD18). J. Exp. Med. 192:193–204.
- Diacovo, T.G., A.R. de Fougerolles, D.F. Bainton, and T.A. Springer. 1994. A functional integrin ligand on the surface of platelets: intercellular adhesion molecule-2. J. Clin. Invest. 94:1243–1251.
- Weber, C., and T.A. Springer. 1997. Neutrophil accumulation on activated, surface-adherent platelets in flow is mediated by interaction of Mac-1 with fibrinogen bound to αIIbβ3 and stimulated by platelet-activating factor. J. Clin. Invest. 100:2085–2093.
- Lampugnani, M.G., and E. Dejana. 1997. Interendothelial junctions: structure, signalling and functional roles. Curr. Opin. Cell Biol. 9:674–682.
- Martin-Padura, I., S. Lostaglio, M. Schneemann, L. Williams, M. Romano, P. Fruscella, C. Panzeri, A. Stoppacciaro, L. Ruco, A. Villa, et al. 1998. Junctional adhesion molecule, a novel member of the immunoglobulin superfamily that distributes at intercellular junctions and modulates monocyte transmigration. J. Cell Biol. 142:117–127.
- Del Maschio, A., A. De Luigi, I. Martin-Padura, M. Brockhaus, T. Bartfai, P. Fruscella, L. Adorini, G. Martino, R. Furlan, M.G. De Simoni, and E. Dejana. 1999. Leukocyte recruitment in the cerebrospinal fluid of mice with experimental meningitis is inhibited by an antibody to junctional adhesion molecule (JAM). J. Exp. Med. 190:1351–1356.
- Ozaki, H., K. Ishii, H. Horiuchi, H. Arai, T. Kawamoto, K. Okawa, A. Iwamatsu, and T. Kita. 1999. Cutting edge: Combined treatment of TNF-α and IFN-γ causes redistribution of junctional adhesion molecule in human endothelial cells. J. Immunol. 163:553–557.
- Naik, U.P., Y.H. Ehrlich, and E. Kornecki. 1995. Mechanism of platelet activation by a stimulatory antibody: cross linking of a novel platelet receptor for mab F11 with the FcγR11 receptor. Biochem. J. 310:155–162.
- Sobocka, M.B., T. Sobocki, P. Banerjee, C. Weiss, J.I. Rushbrook, A.J. Norin, J. Hartwig, M.O. Salifu, M.S. Markell, A. Babinska, et al. 2000. Cloning of the human platelet F11 receptor: a cell adhesion molecule member of the immunoglobulin superfamily involved in platelet aggregation. Blood. 95:2600–2609.
- Naik, U.P., M.U. Naik, K. Eckfeld, P. Martin-Deleon, and J. Spychala. 2001. Characterization and chromosomal localization of JAM-1, a platelet receptor for a stimulatory monoclonal antibody. J. Cell Sci. 114:539–547.
- Malergue, F., F. Galland, F. Martin, P. Mansuelle, M. Aurrand-Lions, and P. Naquet. 1998. A novel immunoglobulin superfamily junctional adhesion molecule expressed by antigen presenting cells, endothelial cells and platelets. Mol. Immunol. 35:1111–1119.
- Williams, L.A., I. Martin-Padura, E. Dejana, N. Hogg, and D.L. Simmons. 1999. Identification and characterisation of human junctional adhesion molecule (JAM). Mol. Immunol. 36:1175–1188.
- Liu, Y., A. Nusrat, F.J. Schnell, T.A. Reaves, S. Walsh, M. Pochet, and C.A. Parkos. 2000. Human junction adhesion molecule regulates tight junction resealing in epithelia. J. Cell Sci. 113:2363–2374.
- Barto, E.S., J.C. Forrest, J.L. Connoly, J.D. Chappell, Y. Liu, F.J. Schnell, A. Nusrat, C.A. Parkos, and T.S. Dermody. 2001. Junctional adhesion molecule is a receptor for reovirus. Cell. 104:441–451.
- Palmeri, D., A. van Zante, C.C. Huang, S. Hemmerich, and S.D. Rosen. 2000. Vascular endothelial junction-associated molecule, a novel member of the immunoglobulin superfamily, is localized to intercellular boundaries of endothelial cells. J. Biol. Chem. 275:19139–19145.
- Cunningham, S.A., M.P. Arrate, J.M. Rodriguez, R.J. Bjercke, P. Vanderslice, A.P. Morris, and T.A. Brock. 2000. A novel protein with homology to the junctional adhesion molecule. Characterization of leukocyte interactions. J. Biol. Chem. 275:34570–34756.
- Santoso, S., J. Lohmeyer, H. Rennich, K.J. Clemetson, and C. Mueller-Eckhardt. 1984. Platelet surface antigens: analysis by monoclonal antibodies. Blut. 48:161–170.
- Santoso, S., R. Kalb, M. Walka, V. Kiefel, C. Mueller-Eckhardt, and P.J. Newman. 1993. The human platelet alloantigens Bra and Brb are associated with a single amino acid polymorphism on glycoprotein Ia (integrin subunit α2). J. Clin. Invest. 92:2427–2432.
- Marx, N., F.J. Neumann, D. Zohlnhofer, T. Dickfeld, A. Fischer, S. Heimerl, and A. Schomig. 1998. Enhancement of monocyte procoagulant activity by adhesion on vascular smooth muscle cells and intercellular adhesion molecule-1-transfected Chinese hamster ovary cells. Circulation. 98:906–911.
- Santoso, S., J. Amrhein, H.A. Hofmann, U.J.H. Sachs, M.M. Walka, H. Kroll, and V. Kiefel. 1999. A point mutation Thr799Met on the α2 integrin leads to the formation of new human platelet alloantigen Sita and affects collagen-induced aggregation. Blood. 94:4103–4111.
- Hölschermann, H., C. Rascher, C. Oelschläger, G. Stapfer, A. Langenstein, A. Staubitz, U. Maus, H. Tillmans, H. Bang, and W. Haberbosch. 2001. Opposite regulation of tissue factor expression by calcineurin in monocytes and endothelial cells. J. Immunol. 1666:7112–7120.
- Chavakis, T., S.M. Kanse, F. Lupu, H.P. Hammes, W. Muller-Esterl, R.A. Pixley, R.W. Colman, and K.T. Preissner. 2000. Different mechanisms define the antiadhesive function of high molecular weight kininogen in integrin- and urokinase receptor dependent interactions. Blood. 96:514–522.
- Chavakis, T., S.M. Kanse, R.A. Pixley, A.E. May, I. Isordia-Salas, R.W. Colman, and K.T. Preissner. 2001. Regulation of leukocyte recruitment by polypeptides derived from high molecular weight kininogen. FASEB J. 15:2365–2376.
- Xia, Z., and M.M. Frojmovic. 1994. Aggregation efficiency of activated normal and fixed platelets in a simple shear field: Effect of shear and fibrinogen occupancy. Biophys. J. 66:2190–2201.
- Ruf, A., M. Pick, V. Deutsch, A. Goldfarb, E.A. Rachmilewitz, A. Bezeaud, M.C. Gullin, and A. Eldor. 1997. The procoagulant activity of red blood cells (RBC) from patients with β thalassemia, determined by annexin V binding, correlates with “in-vivo” platelet activation. Br. J. Haematol. 98:51–56.
- Kasirer-Friede, A., and M.M. Frojmovic. 1998. Ristocetin- and thrombin-induced platelet aggregation at physiological shear rates: differential roles for GPIb and GPIIb-IIIa receptor. Thromb. Haemost. 80:428–436.
- Arrate, M.P., J.M. Rodriguez, T.M. Tran, T.A. Brock, and S.A. Cunningham. 2001. Cloning of human junctional adhesion molecule 3 (JAM3) and its identification as the JAM2 counter-receptor. J. Biol. Chem. 276:45826–45832.
- Bettaieb, A., M. Titeaux, P. Fromont, W. Vainchenker, and P. Bierling. 1995. Characterization of unclustered workshop platelet panel mAb. Leukocyte Typing V. White Cell Differentiation Antigens. S.F. Schlossmann, L. Boumsell, W. Gilks, J.M. Harlan, T. Kishimoto, C. Morimoto, J. Rita, S. Shaw, R. Silverstein, T. Springer, T.F. Tedder, and R.F. Todd, editors. Oxford University Press, Oxford. 1220–1222.
- Ostermann, G., K.S. Weber, A. Zernecke, A. Schroeder, and C. Weber. 2002. JAM-1 is a ligand of the beta-2 integrin LFA-1 involved in transendothelial migration of leukocytes. Nat. Immunol. 3:151–158.
- Rogers, C., E.R. Edelman, and D.I. Simon. 1998. A monoclonal antibody to the β2-leukocyte integrin Mac-1 (CD11b/CD18) reduces intimal thickening after angioplasty or stent implantation in rabbits. Proc. Natl. Acad. Sci. USA. 95:10134–10139.
- Diacovo, T.G., S.J. Roth, J.M. Buccola, D.F. Bainton, and T.A. Springer. 1996. Neutrophil rolling, arrest, and transmigration across activated, surface adherent platelets via sequential of P-selectin and the beta 2-integrin CD11b/CD18. Blood. 88:146–157.
- Evangelista, V., S. Manarini, S. Rotondo, N. Martelli, R. Polischuk, J.L. McGregor, G. de Gaetano, and C. Cerletti. 1996. Platelet/polymorphonuclear leukocyte interaction in dynamic conditions: evidence of adhesion cascade and cross talk between P-selectin and the β2-integrin CD11b/CD18. Blood. 88:4183–4194.
- Kuijper, P.H.M., H.I. Gallardo Torres, J.-W.J. Lammers, J.J. Sixma, L. Koendermann, and J.J. Zwanginga. 1997. Platelet and fibrin deposition at the damaged vessel wall: cooperative substrates for neutrophil adhesion under flow conditions. Blood. 89:166–175.
- Aurrand-Lions, M., C. Johnson-Leger, C. Wong, L. Du Pasquier, and B.A. Imhof. 2001. Heterogeneity of endothelial junctions is reflected by differential expression and specific cellular localization of the three JAM family members. Blood. 98:3699–3707.
- Isacke, C.M., and M.A. Horton. 2000. The Adhesion Molecule. Facts Book. Academic Press, London. 152 pp.
- Xie, J., R. Li, P. Kotovuori, C. Vermont-Desroches, J. Wijdenes, M.A. Arnout, P. Nortamo, and C.G. Gahmberg. 1995. Intercellular adhesion molecule-2 (CD102) binds to the leukocyte integrin CD11b/CD18 through the A domain. J. Immunol. 155:3619–3628.
- Gustafson, E.J., A.H. Schmaier, Y.T. Wachtfogel, N. Kaufman, U. Kucich, and R.W. Colman. 1989. Human neutrophils contain and bind molecular weight kininogen. J. Clin. Invest. 84:28–35.
- Diamond, M.S., R. Alon, C.A. Parkos, M.T. Quinn, and T.A. Springer. 1995. Heparin is an adhesive ligand for the leukocyte integrin Mac-1 (CD11b/CD18). J. Cell Biol. 130:1473–1482.
- Kuijper, P.H., H.I. Gallardo Tores, J.W. Lammers, J.J. Sixma, L. Koenderman, and J.J. Zwanginga. 1998. Platelet associated fibrinogen and ICAM-2 induce firm adhesion of neutrophils under flow conditions. Thromb. Haemost. 80:443–448.
- Silverstein, R., A.S. Asch, and R.L. Nachman. 1989. Glycoprotein IV mediates thrombospondin-dependent platelet-monocyte and platelet-U937 cell adhesion. J. Clin. Invest. 84:546–552.
- Skinner, M.P., C.M. Lucas, G.F. Burns, C.N. Chesterman, and M.C. Berndt. 1991. GMP-140 binds to neutrophils is inhibited by sulphated glycans. J. Biol. Chem. 266:5371–5374.
- Moore, K.L., A. Varki, and R.P. McEver. 1991. GMP-140 binds to a glycoprotein receptor on human neutrophils: evidence for a lectin-like interaction. J. Cell Biol. 112:491–499.
- Ott, I., F.-J. Neumann, M. Gawaz, M. Schmitt, and A. Schomig. 1996. Increased neutrophil-platelet adhesion in patients with unstable angina. Circulation. 94:1239–1246.
- Weyrich, A.S., T.M. McIntyre, R.P. McEver, S.M. Prescott, and G.A. Zimmermann. 1995. Monocyte tethering by P-selectin regulates monocyte chemotatic protein-1 and tumor necrosis factor-α-secretion. J. Clin. Invest. 95:2297–2303.
- Weyrich, A.S., M.R. Elstad, R.P. McEver, T.M. McIntyre, K.L. Moore, J.H. Morrissey, S.M. Prescott, and G.A. Zimmermann. 1996. Activated platelets signal chemokine synthesis by human monocytes. J. Clin. Invest. 97:1525–1534.
- Furman, M.I., S.E. Benoit, M.R. Barnard, C.R. Valeri, M.L. Borbone, R.C. Becker, H.B. Hechtman, and A.D. Michelson. 1998. Increased platelet reactivity and circulating monocyte-platelet aggregates in patients with stable coronary artery disease. J. Am. Coll. Cardiol. 31:352–358.
- Bazzoni, G., O.M. Martinez-Estrada, F. Orsenigo, M. Cordenonsi, S. Citi, and E. Decana. 2000. Interaction of junctional adhesion molecule with the tight junction components ZO-1, cingulin, and occluding. J. Biol. Chem. 275:20520–20526.
- Ebnet, K., C.U. Schulz, M.K. Meyer zu Brickwedel, G.G. Pendl, and D. Vestweber. 2000. Junctional adhesion molecule interacts with PDZ domain-containing proteins AF-6 and ZO-1. J. Biol. Chem. 275:27979–27988.
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