The F11 receptor (F11R/JAM-A) in atherothrombosis: Overexpression of F11R in atherosclerotic plaques

Anna Babinska; Bani M. Azari; Moro O. Salifu; Ruijie Liu; Xian-Cheng Jiang; Malgorzata B. Sobocka; Dorothy Boo; George AI Khoury; Jonathan S. Deitch; Jonathan D. Marmur; Yigal H. Ehrlich; Elizabeth Kornecki

doi:10.1160/TH06-08-0454

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2007; 97(02): 272-281
DOI: 10.1160/TH06-08-0454

Cardiovascular Biology and Cell Signalling

Schattauer GmbH

The F11 receptor (F11R/JAM-A) in atherothrombosis: Overexpression of F11R in atherosclerotic plaques

Authors

Anna Babinska

¹Departments of Anatomy/Cell Biology, SUNY Downstate Medical Center, Brooklyn, New York, USA

²Departments of Medicine, SUNY Downstate Medical Center, Brooklyn, New York, USA
Bani M. Azari

²Departments of Medicine, SUNY Downstate Medical Center, Brooklyn, New York, USA
Moro O. Salifu

²Departments of Medicine, SUNY Downstate Medical Center, Brooklyn, New York, USA
Ruijie Liu

¹Departments of Anatomy/Cell Biology, SUNY Downstate Medical Center, Brooklyn, New York, USA
Xian-Cheng Jiang

¹Departments of Anatomy/Cell Biology, SUNY Downstate Medical Center, Brooklyn, New York, USA
Malgorzata B. Sobocka

²Departments of Medicine, SUNY Downstate Medical Center, Brooklyn, New York, USA
Dorothy Boo

³Departments of Surgery, SUNY Downstate Medical Center, Brooklyn, New York, USA
George AI Khoury

³Departments of Surgery, SUNY Downstate Medical Center, Brooklyn, New York, USA
Jonathan S. Deitch

³Departments of Surgery, SUNY Downstate Medical Center, Brooklyn, New York, USA
Jonathan D. Marmur

²Departments of Medicine, SUNY Downstate Medical Center, Brooklyn, New York, USA
Yigal H. Ehrlich

⁴Program in Neuroscience, City University of New York at Staten Island, New York, New York, USA
Elizabeth Kornecki

¹Departments of Anatomy/Cell Biology, SUNY Downstate Medical Center, Brooklyn, New York, USA

Abstract

Summary

F11R is the gene name for an adhesion protein, called the F11-receptor, aka JAM-A, which under normal physiological conditions is expressed constitutively on the surface of platelets and localized within tight junctions of endothelial cells (EC). Previous studies of the interactions between human platelets and EC suggested that F11R/JAM-A plays a crucial role in inflammatory thrombosis and atherosclerosis. The study reported here obtained in-vivo confirmation of this conclusion by investigating F11R/JAM-A protein and mRNA in patients with aortic and peripheral vascular disease and in an animal model of atherosclerosis. Molecular and immunofluorescence determinations revealed very high levels of F11R/JAM-A mRNA and F11R/JAM-A protein in atherosclerotic plaques of cardiovascular patients. Similar results were obtained with 12-week-old atherosclerosis-prone apoE-/- mice, an age in which atherosclerotic plaques are well established. Enhanced expression of the F11R/JAM-A message in cultured EC from human aortic and venous vessels was observed following exposure of the cells to cytokines. Determinations of platelet adhesion to cultured EC inflamed by combined cytokine treatment in the presence of F11R/JAM-A – antagonists provided data indicating that de novo expression of F11R/JAM-A on the luminal surface of inflamed EC has an important role in the conversion of EC to a thrombogenic surface. Further studies of these interactions under flow conditions and under in-vivo settings could provide a final proof of a causal role for F11R/JAM-A in the initiation of thrombosis. Based on our invitro and in-vivo studies to date, we propose that therapeutic drugs which antagonize the function of F11R/JAM-A should be tested as novel means for the prevention and treatment of atherosclerosis, heart attacks and stroke.

Keywords

F11R - F11 receptor - F11R/JAM-A - inflammatory thrombosis - atherosclerosis - atherothrombosis

Full Text

References

References
1 Kornecki E, Walkowiak B, Naik UP. et al. Activation of human platelets by a stimulatory monoclonal antibody. J Biol Chem 1990; 265: 10042-10048.
2 Sobocka MB, Sobocki T, Babinska A. et al. Signaling pathways of the F11 receptor (F11R; a.k.a. JAM-1, JAM-A in human platelets: F11R dimerization, phosphorylation and complex formation with the integrin GPIIIa. J Recept SignalTransduct Res 2004; 24: 85-105.
3 Wang F, Naik UP, Ehrlich YH. et al. Stimulatory antibody-induced activation and selective translocation of protein kinase C isoenzymes in human platelets. Biochem J 1995; 311: 401-406.
4 Naik UP, Ehrlich YH, Kornecki E. Mechanisms of platelet activation by a stimulatory antibody: crosslinking of a novel platelet receptor for M.Ab.F11 with the Fc γ RII receptor. Biochem J 1995; 311: 155-162.
5 Babinska A, Kedees MH, Athar H. et al. Two regions of the human platelet F11-receptor (F11R) are critical for platelet aggregation, potentiation and adhesion. Thromb Haemost 2002; 87: 712-721.
6 Babinska A, Kedees MH, Athar H. et al. F11-receptor (F11/JAM) mediates platelet adhesion to endothelial cells: role in inflammatory thrombosis. Thromb Haemost 2002; 88: 843-850.
7 Kedees MH, Babinska A, Swiatkowska M. et al. Expression of a recombinant protein of the platelet F11 receptor (F11R) (JAM-1/JAM-A) in insect cells: F11R is naturally phosphorylated in the extracellular domain. Platelets 2005; 16: 99-110.
8 Wagner DD, Burger PC. Platelets in inflammation and thrombosis. Arterioscler Thromb Vasc Biol 2003; 23: 2131-2137.
9 Sobocki T, Sobocka MB, Babinska A. et al. Genomic structure, organization and promoter analysis of the human F11R/F11 receptor/junctional adhesion molecule-1/JAM-A. Gene 2006; 17: 128-144.
10 Bradley JR, Pober JS. Prolonged cytokine exposure causes a dynamic redistribution of endothelial cell adhesion molecules to intercellular junctions. Lab Invest 1996; 75: 463-472.
11 Romer LH, McLean NV, Yan HC. et al. IFN-gamma and TNF-alpha induce redistribution of PECAM-1 (CD31) on human endothelial cells. J Immunology 1995; 154: 6582-6592.
12 O’Brien KD, Allen MD, McDonald TO. et al. Vascular cell adhesion molecule-1 is expressed in human coronary atherosclerotic plaques. Implications for the mode of progression of advanced coronary artery disease. J Clin Invest 1993; 92: 945-951.
13 Poston RN, Haskard DO, Coucher JR. et al. Expression of intercellular adhesion molecule-1 in atherosclerotic plaques. Am J Pathol 1992; 140: 665-673.
14 Printeseva OY, Peclo MM, Gown AM. Various cell types in human atherosclerotic lesions express ICAM-2. Further immunocytochemical and immunochemical studies employing monoclonal antibody 10F3. Am J Pathol 1992; 140: 889-896.
15 Zibara K, Chignier E, Covacho C. et al. Modulation of expression of endothelial intercellular adhesion molecule- 1, platelet-endothelial cell adhesion molecule-1, and vascular cell adhesion molecule-1 in aortic arch lesions of apolipoprotein E-deficient compared with wild-type mice. Arterioscler Thromb Vasc Biol 2000; 20: 2288-2306.
16 Sobocka MB, Sobocki T, Banerjee P. et al. Cloning of the human platelet F11 receptor: a cell adhesion molecule member of the immunoglobulin superfamily involved in platelet aggregation. Blood 2000; 95: 2600-2609.
17 Ozaki H, Ishii K, Horiuchi H. et al. Combined treatment of TNF-α and INF-γ causes redistribution of junctional adhesion molecule in human endothelial cells. J Immunol 1999; 163: 553-557.
18 Ostermann G, Fraemohs L, Baltus T. et al. Involvement of JAM-A in mononuclear cell recruitment on inflamed or atherosclerotic endothelium. Inhibition by soluble JAM-A. Arterioscler Thromb Vasc Biol 2005; 25: 729-735.
19 Pajukanta P, Lilja HE, Sinsheimer JS. et al. Familial combined hyperlipidemia is associated with upstream transcription factor 1 (USF1). Nature Genet 2004; 36: 371-376.
20 Papapyridonos M, Smith A, Burnand KG. et al. Novel candidate genes in unstable areas of human atherosclerotic plaques. Arterioscler Thromb Vasc Biol 2006; 26: 1837-1844.
21 Prophet EB, Mills B, Arrington JB. et al. eds. Washington, DC: American Registry of Pathology; 1992. Armed Forces Institute of Pathology Laboratory Methods in Histotechnology.
22 Rogers WJ, Prichard JW, Hu Y-L. et al. Characterization of signal properties in atherosclerotic plaque components by intravascular MRI. Arterioscler Thromb Vasc Biol 2000; 20: 1824-1830.
23 Gawaz M, Langer H, May AE. Platelets in inflammation and atherogenesis. J Clin Invest 2005; 115: 3378-3384.
24 Theilmeier G, Michiels C, Spaepen E. et al. Endothelial von Willebrand factor recruits platelets to atherosclerosis-prone sites in response to hypercholesterolemia. Blood 2002; 99: 4486-4493.
25 Massberg S, Brand K, Gruner S. et al. A critical role of platelet adhesion in the initiation of atherosclerotic lesion formation. J Exp Med 2002; 196: 887-896.
26 Cines DB, Pollak ES, Buck CA. et al. Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood 1998; 91: 3527-3561.
27 Karsan A, Harlan JM. The blood vessel wall. In: Hematology: Basic Principles and Practice, 3 rd Ed. Elsevier; Oxford: 2000: 1770-1782.
28 May AE, Neumann FJ, Preissner KT. The relevance of blood cell-vessel wall adhesive interactions for vascular thrombotic disease. Thromb Haemost 1999; 82: 962-970.
29 Diquelou A, Dupoy D, Gaspin D. et al. Relationship between endothelial tissue factor and thrombogenesis under blood flow conditions. Thromb Haemost 1995; 74: 778-783.
30 André P, Denis CV, Ware J. et al. Platelets adhere to and translocate on von Willebrand factor presented by endothelium in stimulated veins. Blood 2000; 96: 3322-3328.
31 Frenette PS, Johnson RC, Hynes RO. et al. Platelets roll on stimulated endothelium in vivo: an interaction mediated by P-selectin. PNAS 1995; 92: 7450-7454.
32 Frenette PS, Denis CV, Weiss L. et al. P-selectin glycoprotein ligand 1 (PSGL-1) is expressed on platelets and can mediate platelet-endothelial interactions in vivo. J Exp Med 2000; 191: 1413-1422.
33 Gurubhagavatula I, Amrani Y, Practico D. et al. Engagement of human PECAM-1 (CD31) on human endothelial cells increases intracellular calcium ion concentration and stimulates prostacyclin release. J Clin Invest 1998; 101: 212-222.
34 Rosenblum WI, Nelson GH, Wornley B. et al. Role of platelet-endothelial cell adhesion molecule (PECAM) in platelet adhesion/aggregation over injured but not denuded endothelium in vivo and ex vivo. Stroke 1995; 27: 709-711.
35 Sun J, Williams J, Yan H-C. et al. Individually distinct Ig homology domains in PECAM-1 regulate homophilic binding and modulate receptor affinity. J Biol Chem 1996; 271: 18561-18570.
36 Bombeli T, Schwartz BR, Harlan JM. Endothelial cells undergoing apoptosis become proadhesive for nonactivated platelets. Blood 1999; 93: 3831-3838.
37 Romo GM, Dong JF, Schade AJ. et al. The glycoprotein Ib-IX-V complex is a platelet counterpart for P-selectin. J Exp Med 1999; 190: 803-813.
38 Young JL, Libby P, Schonbeck U. Cytokines in the pathogenesis of atherosclerosis. Thromb Haemost 2002; 88: 554-567.
39 Plump AS, Smith JD, Hayek T. et al. Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells. Cell 1992; 16: 343-353.