Abstract
The splenic sinus endothelium regulates the passage of blood cells through the splenic cord. The goal of the present study was to assess the localization of vascular endothelial (VE)-cadherin, β-catenin, and p120-catenin in the sinus endothelial cells of rat spleen and to characterize the presence and distribution of adherens junction formation mediated by the cadherin-catenin complex. Immunofluorescent microscopy of tissue cryosections demonstrated that VE-cadherin, β-catenin, and p120-catenin were localized in the junctional regions of adjacent endothelial cells. Double-staining immunofluorescent microscopy for VE-cadherin and β-catenin revealed colocalization at junctional regions. Transmission electron microscopy of thin sections of sinus endothelial cells treated with Triton X-100 clearly showed adherens junctions within the plasma membrane. Adherens junctions were located at various levels in the lateral membranes of adjacent endothelial cells regardless of the presence or absence of underlying ring fibers. Immunogold electron microscopy revealed VE-cadherin, β-catenin, and p120-catenin in the juxtaposed junctional membranes of adjacent sinus endothelial cells. Double-staining immunogold microscopy for VE-cadherin and β-catenin and for VE-cadherin and p120-catenin demonstrated colocalization to the junctional membranes of adjacent endothelial cells. Immunolabeling was evident at various levels in the lateral junctional membranes and was intermittently observed in the sinus endothelium. These data suggest that adherens junctions, whose formation appears to be mediated by VE-cadherin-catenin complexes, probably regulate the passage of blood cells through the spleen.
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Adamson RH, Liu B, Fry GN, Rubin LL, Curry FE (1998) Microvascular permeability and number of tight junctions are modulated by cAMP. Am J Physiol 274:H1885–H1894
Ahmmed GU, Mehta D, Vogel S, Holinstat M, Paria BC, Tiruppathi C, Malik AB (2004) Protein kinase C alpha phospholylates the transient receptor potential channel-1 (TRPC-1) and regulates store operated Ca2+ entry in endothelial cells. J Biol Chem 279:20941–20949
Alexander JS, Jackson SA, Chaney E, Kevil CG, Haselton FR (1998) The role of cadherin endocytosis in endothelial barrier regulation: involvement of protein kinase C and actin-cadherin interactions. Inflammation 22:419–433
Ali J, Liao F, Martens E, Muller WA (1997) Vascular endothelial cadherin (VE-cadherin): cloning and role in endothelial cell-cell adhesion. Microcirculation 4:267–277
Allport JR, Ding H, Collins T, Gerritsen ME, Luscinskas FW (1997) Endothelial-dependent mechanisms regulate leukocyte transmigration: a process involving the proteasome and disruption of vascular endothelial-cadherin complex at endothelial cell-to-cell junctions. J Ext Med 186:517–527
Angst BD, Marcozzi C, Magee AI (2001) The cadherin superfamily: diversity in form and function. J Cell Sci 114:629–641
Aono S, Nakagawa S, Reynolds AB, Takeichi M (1999) p120(ctn) acts as an inhibitory regulator of cadherin function in colon carcinoma cells. J Cell Biol 145:551–562
Brakemeier S, Eichler I, Hopp H, Kohler R, Hoyer J (2002) Up-regulation of endothelial stretch-activated cation channels by fluid shear stress. Cardiovasc Res 53:209–218
Breviario F, Caveda L, Corada M, Martin-Padura I, Navarro P, Golay J, Introna M, Gulino D, Lampugnani MG, Dejana E (1995) Functional properties of human vascular endothelial cadherin (7B4/cadherin-5), an endothelium-specific cadherin. Arterioscler Thromb Vasc Biol 15:1229–1239
Brough GH, Wu S, Cioffi D, Moore TM, Li M, Dean N, Stevens T (2001) Contribution of endogenously expressed Trp1 to a Ca2+-selective, store-operated Ca2+ entry pathway. FASEB J 15:1727–1738
Carmeliet P, Lampugnani MG, Moons L, Breviario F, Compernolle V, Bono F, Balconi G, Spagnuolo R, Oostuyse B, Dewerchin M, Zanetti A, Angellilo A, Mattot V, Nuyens D, Lutgens E, Clotman F, Ruiter MC de, Gittenberger-de Groot A, Poelmann R, Lupu F, Herbert JM, Collen D, Dejana E (1999) Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis. Cell 98:147–157
Caveda L, Martin-Padura I, Navarro P, Breviario F, Corada M, Gulino D, Lampugnani MG, Dejana E (1996) Inhibition of cultured cell growth by vascular endothelial cadherin (cadherin-5/VE-cadherin). J Clin Invest 98:886–893
Chen LT, Weiss L (1972) Electron microscopy of the red pulp of the human spleen. Am J Anat 134:425–457
Corada M, Mariotti M, Thurston G, Smith K, Kunkel R, Brockhaus M, Lampugnani MG, Martin-Padura I, Stoppacciaro A, Ruco L, McDonald DM, Ward PA, Dejana E (1999) Vascular endothelial-cadherin is an important determinant of microvascular integrity in vivo. Proc Natl Acad Sci U S A 96:9815–9820
Corada M, Liao F, Lindgren M, Lampugnani MG, Breviario F, Frank R, Muller WA, Hicklin DJ, Bohlen P, Dejana E (2001) Monoclonal antibodies directed to different regions of vascular endothelial cadherin extracellular domain affect adhesion and clustering of the protein and modulate endothelial permeability. Blood 97:1679–1684
Del Maschio A, Zanetti A, Corada M, Rival Y, Ruco L, Lampugnani MG, Dejana E (1996) Polymorphonuclear leukocyte adhesion triggers the disorganization of endothelial cell-to-cell adherens junctions. J Cell Biol 135:497–510
Drenckhahn D, Wagner J (1986) Stress fibers in the splenic sinus endothelium in situ: molecular structure, relationship to the extracellular matrix, and contractility. J Cell Biol 102:1738–1747
Ferber A, Yaen C, Sarmiento E, Martinez J (2002) An octapeptide in the juxtamembrane domain of VE-cadherin is important for p120ctn binding and cell proliferation. Exp Cell Res 274:35–44
Gumbiner BM (1995) Signal transduction of beta-catenin. Curr Opin Cell Biol 7:634–640
Haselton FR, Heimark RL (1997) Role of cadherin-5 and 13 in the aortic endothelial barrier. J Cell Physiol 171:243–251
Heusermann U, Stutte HJ (1974) Intercellular junctions of sinus lining cells in the human spleen. Cell Tissue Res 151:337–342
Hinck L, Nathke IS, Papkoff J, Nelson WJ (1994) β-Catenin: a common target for the regulation of cell adhesion by wnt-1 and Src signaling pathways. Trends Biochem Sci 19:538–542
Hirasawa Y, Tokuhiro H (1970) Electron microscopic studies on the normal human spleen: especially on the red pulp and the reticulo-endothelial cells. Blood 35:201–212
Hordijk PL, Anthony E, Mul FP, Rientsma R, Oomen LC, Roos D (1999) Vascular-endothelial-cadherin modulates endothelial monolayer permeability. J Cell Sci 112:1915–1923
Iyer S, Ferreri DM, Decocco N, Minnear FL, Vincent PA (2004) VE-cadherin-p120 interaction is required for maintenance of endothelial barrier function. Am J Physiol Lung Cell Mol Physiol 286:L1143–L1153
Kaiserling E, Wolburg H, Banks P (1989) Freeze-fracture investigation of the red pulp of human spleen. Virchows Arch B Cell Pathol 58:15–23
Kevil CG, Payne DK, Mire E, Alexander JS (1998) Vascular permeability factor/vascular endothelial cell growth factor-mediated permeability occurs through disorganization of endothelial junctional proteins. J Biol Chem 273:15099–15103
Lampugnani MG, Resnati M, Raiteri M, Pigott R, Pisacane A, Houen G, Ruco LP, Dejana E (1992) A novel endothelial-specific membrane protein is a marker of cell-cell contacts. J Cell Biol 118:1511–1522
Lampugnani MG, Corada M, Caveda L, Breviario F, Ayalon O, Geiger B, Dejana E (1995) The molecular organization of endothelial cell to cell junctions: differential association of plakoglobin, β-catenin, α-catenin with vascular endothelial cadherin (VE-cadherin). J Cell Biol 129:203–217
Navarro P, Caveda L, Breviario F, Mandoteanu I, Lampugnani MG, Dejana E (1995) Catenin-dependent and -independent functions of vascular endothelial cadherin. J Biol Chem 270:30965–30972
Ohkubo T, Ozawa M (1999) p120(ctn) binds to the membrane-proximal region of the E-cadherin cytoplasmic domain and is involved in modulation of adhesion activity. J Cell Biol 274:21409–21415
Paria BC, Malik AB, Tiruppathi C (2002) Direct relationship between trp1 expression and Ca2+ signaling in human endothelial cells. FASEB J 16:A673–A678
Ratcliffe MJ, Smales C, Staddon JM (1999) Dephosphorylation of the catenins p120 and p100 in endothelial cells in response to inflammatory stimuli. Biochem J 338:471–478
Shaw SK, Bamba PS, Perkins BN, Luscinskas FW (2001) Real-time imaging of vascular endothelial-cadherin during leukocyte transmigration across endothelium. J Immunol 167:2323–2330
Thomas CE (1967) An electron and light-microscopic study of sinus structure in perfused rabbit and dog spleen. Am J Anat 120:527–552
Tinsley JH, Wu MH, Ma W, Taulman AC, Yuan SY (1999) Activated neutrophils induce hyperpermeability and phosphorylation of adherence junction proteins in coronary venular endothelial cells. J Biol Chem 274:24930–24934
Tinsley JH, Ustinova EE, Xu W, Yuan SY (2002) Src-dependent, neutrophil-mediated vascular hyperpermeability and β-catenin modification. Am J Physiol Cell Physiol 283:C1745–C1751
Tiruppathi C, Minshall RD, Paria BC, Vogel SM, Malik AB (2002) Role of Ca2+ signaling in the regulation of endothelial permeability. Vascul Pharmacol 39:173–185
Uehara K (2005) Localization of TRPC1 channel in the sinus endothelial cells of rat spleen. Histochem Cell Biol 123:347–356
Uehara K, Miyoshi M (1997) Junctions between the sinus endothelial cells of rat spleen. Cell Tissue Res 287:187–192
Uehara K, Miyoshi M (1999a) Stress fiber networks in sinus endothelial cells in the rat spleen. Anat Rec 254:22–27
Uehara K, Miyoshi M (1999b) Tight junction of sinus endothelial cells of the rat spleen. Tissue Cell 31:555–560
Uehara K, Onoue H, Jeyakumar LH, Fleischer S, Uehara A (2004) Localization ryanodine receptor 3 in the sinus endothelial cells of the rat spleen. Cell Tissue Res 317:137–145
Ukropec JA, Hollinger MK, Salva SM, Woolkalis MJ (2000) SHP2 association with VE-cadherin complexes in human endothelial cells is regulated by thrombin. J Biol Chem 275:5983–5986
Usatyuk PV, Fomin VP, Shi S, Garcia JG, Schaphorst K, Natarajan V (2003) Role of Ca2+ in diperoxovanadate-induced cytoskeletal remodeling and endothelial cell barrier function. Am J Physiol Lung Mol Physiol 285:L1006–L1007
Winter MC, Kamath AM, Ries DR, Shasby SS, Chen YT, Shasby DM (1999) Histamine alters cadherin-mediated sites of endothelial adhesion. Am J Physiol 277:L988–L995
Wong EY, Morgan L, Smaples C, Lang P, Gubby SE, Staddon JM (2000) Vascular endothelial growth factor stimulates dephosphorylation of the catenins p120 and p100 in endothelial cells. Biochem J 346:209–216
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This work was supported by a Grant-in-Aid for Scientific Research (C), Japan
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Uehara, K. Distribution of adherens junction mediated by VE-cadherin complex in rat spleen sinus endothelial cells. Cell Tissue Res 323, 417–424 (2006). https://doi.org/10.1007/s00441-005-0064-5
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DOI: https://doi.org/10.1007/s00441-005-0064-5