Abstract
In this immunohistochemical light microscopic study we applied a panel of monoclonal antibodies to study the expression pattern of adhesion molecules in normal human conjunctiva from 15 patients. The molecules we analyzed included the VLA-family VLA-1-6, the leukocyte integrins LFA-1, Mac-1 and p150,95, the immunoglobulins LFA-3, CD2, ICAM-1 and VCAM-1 and the selectin ELAM-1. Our results show that only VLA-2, VLA-3, LFA-3, and the VLA-α 6 subunit are expressed on the epithelium. A strongly basal accentuation of the VLA-α6 subunit indicates its possible relevance in anchoring the epithelium at the substantia propria. Intraepithelial T cells were VLA-1, VLA-5, LFA-1, and CD2 positive. Endothelial cells expressed VLA-1, VLA-2, VLA-3, VLA-5, VLA-a6, ICAM-1, and LFA-3. ELAM-1 was seen only in specimens from five patients. Interestingly, mast cells were positive for VLA-3 and VLA-5, both of which are receptors for fibronectin, indicating that these integrins play an important role in mast cell function. Our study builds the basis for further investigations in adhesion molecules in conjunctival diseases.
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Adams JC, Watt FM (1989) Fibronectin inhibits the terminal differentiation of human keratinocytes. Nature 340:307–309
Altieri DC, Agbanyo F, Plescia J, Ginsberg MH, Edgington TS, Plow EF (1990) A unique recognition site mediates the interaction of fibrinogen with the leukocyte integrin Mac-1 (CDllb/CD18). J Biol Chem 265:12119–12122
Anderson DC, Springer TA (1987) Leukocyte adhesion defiency: an inherited defect in the Mac-1, LFA-1, and p150,95 glycoproteins. Annu Rev Med 38:175–194
Bevilacqua MP, Stengelin S, Gimbrone MA Jr., Seed B (1989) Endothelial leukocyte adhesion molecules 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins. Science 243:1160–1165
Bierer BE, Peterson A, Gorga JC, Herrmann SH, Burakoff SJ (1988) Synergistic T cell activation via the physiological ligands for CD2 and the T cell receptor. J Exp Med 168:1145–1156
Carlos TM, Schwartz BR, Kovach NL, Yee E, Rosso M, Osborn L, Chi-Rosso G, Newman B, Lobb R, Harlan JM (1990) Vascular adhesion molecule-1 mediates lymphocyte adherence to cytokine-activated cultured human endothelial cells. Blood 75:965–970
Carter WG, Wayner EA, Bouchard TS, Kauer P (1990) The role of integrins α2 β 1 and a3β1 in cell-cell and cell-substrat adhesion of human epidermal cells. J Cell Biol 110:1387–1404
Choy M-Y, Richman PI, Horton MA, MacDonald TT (1990) Expression of the VLA family of integrins in human intestine. J Pathol 160:35–40
Clark RAF (1990) Fibronectin matrix deposition and fibronectin receptor expression in healing and normal skin. J Invest Dermatol [Suppl] 6:128–134
Corrigan CJ, Hartnell A, Kay AB (1988) T-lymphocyte activation in acute severe asthma. Lancet 1:1129–1131
Donaldson DS, Mahan JT (1988) Keratinocyte migration and the extracellular matrix. J Invest Dermatol 90:623–628
Dustin ML, Rothlein R, Bhan AK, Dinarello CA, Springer TA (1986) Induction by IL-1 and interferon, tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1). J Immunol 137:245–254
Dustin ML, Sanders ME, Shaw S, Springer TA (1987) Purified lymphocyte function-associated antigen 3 binds to CD2 and mediates T lymphocyte adhesion. J Exp Med 165:677–692
Gehlsen KR, Dickerson K, Argraves WS, Engvall E, Ruoslahti E (1989) Subunit structure of a laminin-binding integrin and localisation of its binding site on laminin. J Biol Chem 264:19034–19038
Griffiths CEM, Barker JNWN, Kunkel S, Nickoloff BJ (1991) Modulation of leukocyte adhesion molecules, a T-cell chemotaxin (IL-8) and a regulatory cytokine (TNF-a) in allergic contact dermatitis (thus dermatitis). Br J Dermatol 124:519–526
Hall DE, Reichardt LF, Crowley E, Holley B, Moezzi H, Sonnenberg A, Damsky CH (1990) The αl/β 1 and α6/β 1 integrin heterodimers mediate cell attachment to distinct sites on laminin. J Cell Biol 110:2175–2184
Hemler ME, Jacobson JG (1987) Cell matrix adhesion related proteins VLA-1 and VLA-2: regulation of expression on T-cells. J Immunol 138:2941–2948
Hemler ME, Jacobson JG, Brenner MB, Mann D, Strominger JL (1985) VLA-1: a T cell surface antigen which defines a novel late stage of human T cell activation. Eur J Immunol 1:502–508
Hemler ME, Elices MJ, Parker C, Takada Y (1990) Structure of the integrin VLA-4 and its cell-cell and cell-matrix adhesion functions. Immunol Rev 114:45–66
Hynes RO (1987) Integrins: a family of cell surface receptors. Cell 48:549–554
Johnston GI, Cook RG, McEver RP (1989) Cloning of GMP140, a granule membrane protein of platelets and endothelium: sequence similarity to proteins involved in cell adhesion and inflammation. Cell 56:1033–1044
Kajiji S, Tamura RN, Quaranta V (1989) A novel integrin (αc β 4) from human epithel suggests a fourth family of integrin adhesion receptors. EMBO J 8:673–680
Kaufmann R, Klein CE, Frösch D, Westphal C, Weber L (1989) Integrin VLA-3: Ultrastructural localisation at cell-cell contact sites of human cell cultures. J Cell Biol 109:1807–1815
Kirchhofer DL, Languino R, Ruoslahti E, Pierschbacher MD (1990) α2β1 integrins from different cell types show different binding specificities. J Biol Chem 265:615–618
Kishimoto TK, Larson Corbi AL, Dustin ML, Staunton DE et al. (1989) The leukocyte integrins: LFA-1, Mac-1, and p150,95. Adv Immunol 46:149–182
Konter U, Kellner I, Klein E, Kaufmann R, Mielke V, Sterry W (1989) Adhesion molecules in normal human skin. Arch Dermatol Res 281:454–462
Krenzky AM, Sanchez-Madrid F, Robbins E, Nagy JA, Springer TA, Burakoff SJ (1983) The functional significance, distribution, and structure of LFA-1, LFA-2, LFA-3: cell surface antigens associated with CTL-target interactions. J Immunol 131:611–616
Larson RS, Springer TA (1990) Structure and function of leukocyte integrins. Immunol Rev 114:181–216
Liotta LA, Rao CN, Barsky SH (1983) Tumor invasion and the extracellular matrix. Lab Invest 49:636–649
Mackay CR (1991) Skin-seeking memory T cells. Nature 349:737–738
Marlin SD, Springer TA (1987) Purified intercellular adhesion molecule-1 (ICAM-1) is a ligand for lymphocyte function-associated antigen 1 (LFA-1). Cell 51:813–819
Morgan SJ, Williams JH, Walls AF, Church MK, Holgate ST, McGill JI (1991) Mast cell number and staining characteristics in the normal and allergic human conjunctiva. J Allergy Clin Immunol 87:111–116
Nishida T, Nakagawa S, Awata T, Ohashi Y, Wantanaba K, Manabe R (1983) Fibronectin promotes epithelial migration of cultured rabbit cornea in situ. J Cell Biol 97:1653–1657
Picker LJ, Kishimoto TK, Smith CW, Warnock RA, Butcher EC (1991) ELAM-1 is an adhesion molecules for skin-homing T cells. Nature 349:796–799
Pytela R, Pierschbacher MD, Ruoslahti E (1985) A 125/115kDa cell surface receptor specific for vitronectin interacts with the arginine-glycine-asparic acid adhesion sequence derived from fibronectin. Proc Nail Acad Sci USA 82:5766–5770
Pytela R, Pierschbacher MD, Ginsberg MH, Plow EF, Ruoslahti E (1986) Platelet membrane glycoprotein Ilb/IIa: member of a family of arg-gly-asp-specific adhesion receptors. Science 231:1559–1562
Rice GE, Bevilacqua MP (1989) An inducible endothelial cell surface glycoprotein mediates melanoma adhesion. Science 246:1303–1306
Ruoslahti E, Giancotti FG (1989) Integrins and tumor dissemination. Cancer Cells 1:119–126
Saltini C, Hemler ME, Crystal RG (1988) T-lymphocytes compartmentlised on the epithelial surface of the lower respiratory tract express the very late activation complex VLA-1. Clin Immunol Immunopathol 46:221–233
Sanchez-Madrid F, De Landazuri MO, Morago G, Cebrian M, Avecedo A, Bernabeu C (1986) VLA-3: a novel polypeptide association within the VLA molecular complex: cell distribution and biochemical characterization. Eur J Immunol 16:1343–1349
Shimizu Y, Shaw S, Graber N, Venkat Gopal T, Horgan KJ, van Seventer GA, Newman W (1991) Activation-independent binding of human memory T cells to adhesion molecule ELAM-1. Nature 349:799–802
Sonnenberg A, Modderman PW, Hogervorst F (1988) Laminin receptors on platelets is the integrin VLA-6. Nature 336:487–489
Sonnenberg A, Calafat J, Janssen H, Daams H, Raaij-Helmet LM van der, Falcioni R, Kennel SJ, Aplin JD, Baker J, Loizidou M et al. (1991) In tegrin alpha 6/beta 4 complex is located in hemidesmosomes, suggesting a major role in epidermal cellbasement membrane adhesion. J Cell Biol 113:907–917
Springer TA (1990) Sensation and regulation of interactions with the extracellular environment: the cell biology of lymphocyte adhesion receptors. Annu Rev Cell Biol 6:359–402
Springer TA, Dustin ML, Kishimoto TK, Marlin SD (1987) The lymphocyte function-associated LFA-1, CD2, and LFA-3 molecules: cell adhesion receptors of the immune system. Annu Rev Immunol 5:223–252
Staunton DE, Marlin SD, Stratowa C, Dustin ML, Springer TA (1988) Primary structure of ICAM-1 demonstrates interaction between members of the immunoglobulin and integrin supergene families. Cell 1988 52:925–933
Staunton DE, Dustin ML, Springer TA (1989) Functional cloning of ICAM-2, a cell adhesion ligand for LFA-1 homologous to ICAM-1. Nature 339:61–64
Stoolman LM (1989) Adhesion molecules controlling lymphocyte migration. Cell 56:907–910
Takada Y, Huang C, Hemler ME (1987) Fibronectin receptor structures in the VLA family of heterodimers. Nature 326:607–609
Wayner EA, Carter WG (1987) Identification of multiple cell adhesion receptors for collagen and fibronectin in human flbrosarcoma cells possessing unique a and common β subunits. J Cell Biol 105:1873–1884
Wayner EA, Garcia-Pardo A, Humphries MJ, McDonald JA, Carter WG (1989) Identification and characterization of the T-lymphocyte adhesion receptor for an alternative cell attachment domain (CS-1) in plasma fibronectin. J Cell Biol 109:1321–1330
Williams AF, Barclay AN (1988) The immunoglobulin superfamily domains for cell surface recognition. Annu Rev Immunol 6:381–405
Wright SD, Craigmyle LS, Silverstein S (1983) Fibronectin and serum amyloid P component stimulate C3b- and C3bi- mediated phagocytosis in cultured human monocytes. J Exp Med 158:1338–1343
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Vorkauf, M., Duncker, G., Nölle, B. et al. Adhesion molecules in normal human conjunctiva An immunohistological study using monoclonal antibodies. Graefe's Arch Clin Exp Ophthalmol 231, 323–330 (1993). https://doi.org/10.1007/BF00919028
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DOI: https://doi.org/10.1007/BF00919028