Skip to main content
SpringerLink
Log in

Localization of the cytoadhesin integrins in the human cornea

An immunohistochemical study using monoclonal antibodies

  • Laboratory investigations
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

Abstract

Cell-matrix interactions play a fundamental role in normal and pathological conditions. They can be mediated by the cytoadhesin subgroup of the integrin superfamily of adhesion molecules. Its members include the vitronectin receptor (VNR) and the platelet glycoprotein IIb/IIIa (GP IIb/IIIa). Both receptors are composed of an α-chain (αv and aIIb, respectively) coupled to a β3-chain. Using in situ immunohistochemistry and monoclonal antibodies, the authors studied the distribution of GP IIIa (common β3-chain), GP IIb/IIIa (αIIb-chain) and VNR (αv-chain) in normal and pathological corneal tissues. In the normal cornea, the limbal vascular endothelium was weakly αv-positive. Occasionally, faint and granular staining was seen in the epithelium. In the pathological samples, an upregulated expression of the αv chain was noticed on the corneal epithelium as well as on fibroblasts and corneal endothelium. The aIIb and β3-chains were consistently absent. These data suggest that expression of the VNR-αv- chain in the human cornea is modulated by soluble factors released during inflammation and wound healing. Dissociation of expression of the αv and β3-chains suggests usage of an alternative α-chain by the VNR-αv-chain.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Albelda SM, Buck CA (1990) Integrins and other cell adhesion molecules. FASEB J 4:2868–2880

    CAS  PubMed  Google Scholar 

  2. Athanasou NA, Quinn J, Horton MA, McGee J'OD (1990) New sites of normal vitronectin receptor immunoreactivity detected with osteoclast-reacting monoclonal antibodies 13C2 and 2306. Bone Miner 8:7–22

    Google Scholar 

  3. Bodary SC, McLean JW (1990) The integrin β1 subunit associates with the vitronectin receptor αv subunit to form a novel vitronectin receptor in a human embryonic kidney cell line. J Biol Chem 265:5938–5941

    Google Scholar 

  4. Buck CA, Horwitz AF (1987) Cell surface receptors for extracellular matrix molecules. Ann Rev Cell 13:179–205

    Google Scholar 

  5. Charo IF, Bekaert LS, Phillips DR (1987) Platelet glycoprotein IIb/IIIa-like proteins mediate endothelial cell attachment to adhesive protein and extracellular matrix. J Biol Chem 262:9935–9938

    Google Scholar 

  6. Charo IF, Nannizzi L, Smith JW, Cheresh DA (1990) The vitronectin receptor αvβ3 binds fibronectin and acts in concert with α5β1 in promoting cellular attachment and spreading on fibronectin. J Cell Biol 111:2795–2800

    Google Scholar 

  7. Cheng YF, Kramer RH (1989) Human microvascular endothelial cells express integrin-related complexes that mediate adhesion to the extracellular matrix. J Cell Physiol 139:275–286

    Google Scholar 

  8. Cheresh DA (1987) Human endothelial cells synthesize and express an arg-gly-asp-directed adhesion receptor involved in attachment to fibrinogen and van Willebrand factor. Proc Natl Acad Sci USA 84:6471–6475

    Google Scholar 

  9. Cheresh DA, Spiro RC (1987) Biosynthetic and functional properties of an Arg-Gly-Asp directed receptor involved in human melanoma cell attachment to vitronectin, fibrinogen, and von Willebrand factor. J Biol Chem 262:17703–17711

    Google Scholar 

  10. Cheresh DA, Smith JW, Cooper HM, Quaranta V (1989) A novel vitronectin receptor integrin (αvβx) is responsible for distinct adhesive properties of carcinoma cells. Cell 57:56–69

    Google Scholar 

  11. Dedhar S, Gray V (1990) Isolation of a novel integrin receptor mediating Arg-Gly-Asp-directed cell adhesion to fibronectin and type I collagen from human neuroblastoma cells. Association of a novel β1-related subunit with αv. J Cell Biol 110:2185–2193

    Google Scholar 

  12. Dejana E, Colella S, Conforti G, Abbadini M, Gaboli M, Marchisio PC (1988) Fibronectin and vitronectin regulate the organization of their respective Arg-Gly-Asp adhesion receptors in cultured human endothelial cells. J Cell Biol 107:1215–1223

    Google Scholar 

  13. Dejana E, Languino LR, Colella S, Corbascio GC, Plow E, Ginsberg M, Marchisio PC (1988) The localization of a platelet glycoprotein IIb/IIIa-related protein in endothelial cell adhesion structures. Blood 71:566–572

    Google Scholar 

  14. Fitzgerald LA, Poncz M, Steiner B, Rall SC, Benneth JS, Phillips DR (1987) Comparison of cDNA-derived protein sequences of the human Fibronectin and vitronectin receptor α-subunits and platelet glycoprotein IIb. Biochemistry 26:8158–8165

    Google Scholar 

  15. Fitzgerald LA, Steiner B, Rall SC, Lo SS, Phillips DR (1987) Protein sequence of endothelial glycoprotein IIIa derived from a cDNA clone. J Biol Chem 262:3936–3939

    Google Scholar 

  16. Freed E, Gailit J, Geer P van der, Ruoslahti E, Hunter T (1989) A novel integrin β subunit is associated with the vitronectin receptor α subunit (αv) in a human osteosarcoma cell line and is substrate for protein kinase C. EMBO J 8:2955–2965

    Google Scholar 

  17. Ginsberg MH, Loftus JC, Plow EF (1988) Cytoadhesins, integrins and platelets. Thromb Haemost 59:1–6

    Google Scholar 

  18. Hayashi K, Frangeih G, Wolf G, Kenyon KR (1989) Expression of transgrowing growth factor-β in wound healing of vitamin A-deficient rat corneas. Invest Ophthalmol Vis Sci 30:239–247

    Google Scholar 

  19. Hayman EG, Pierschbacher MD, Öhgren Y, Ruoslahti E (1983) Serum spreading factor (vitronectin) is present at the cell surface and in tissues. Proc Nail Acad Sci USA 80:4003–4007

    Google Scholar 

  20. Hemler ME (1990) VLA-proteins in the Integrin family: structures, functions and their role on leucocytes. Ann Rev Immunol 8:365–400

    Google Scholar 

  21. Hynes RO (1987) Integrins: a family of cell surface receptors. Cell 48:549–554

    Article  CAS  PubMed  Google Scholar 

  22. Ignatius MJ, Large TH, Houde M, Tawil JW, Burton A, Esch F, Carbonetto S, Reichardt LF (1990) Molecular cloning of the rat integrin α1-subunit: a receptor for laminin and collagen. J Cell Biol 111:709–720

    Google Scholar 

  23. Ignotz RA, Heino J, Massagué J (1989) Regulation of cell adhesion receptors by transgrowing growth factor-β: regulation of vitronectin receptor and LFA-1. J Biol Chem 264:389–392

    Google Scholar 

  24. Kay EP (1986) Rabbit corneal endothelial cells modulated by polymorphonuclear leucocytes are fibroblasts: comparison with keratocytes. Invest Ophthalmol Vis Sci 27:891–897

    Google Scholar 

  25. Kishimoto TK, Larson RS, Corbi AL, Dustin ML, Staunton DE, Springer TA (1989) The leucocyte integrins. Adv Immunol 46:149–182

    Google Scholar 

  26. Kramer RH, Cheng YF, Clyman R (1990) Human microvascular endothelial cells use β1 and β3, Integrin receptor complexes to attach to laminin. J Cell Biol 111:1233–1243

    Google Scholar 

  27. Lauweryns B, van den Oord JJ, Volpes R, Foets B, Missotten L (1991) Distribution of very late activation integrins in the human cornea: an immunohistochemical study using monoclonal antibodies. Invest Ophthalmol Vis Sci 32:2079–2085

    Google Scholar 

  28. Lawler J, Weinstein R, Hynes RO (1988) Cell attachment to thrombospondin: role of Arg-Gly-Asp, calcium and integrin receptors. J Cell Biol 107:2351–2361

    Google Scholar 

  29. Nazzarro V, Berti E, Cerri A, Brusasco A, Cavalli R, Caputo R (1990) Expression of integrins in junctional and dystrophic epidermolysis bullosa. J Invest Dermatol 95:60–64

    Google Scholar 

  30. Phillips DR, Charo IF, Parise LV, Fitzgerald LA (1988) The platelet membrane glycoprotein IIb/IIIa complex. Blood 71:831–843

    Google Scholar 

  31. Podack ER, Preissner KT, Müller Eberhard HJ (1984) Inhibition of C9 polymerisation within the SC5b-9 complex of complement by S-protein. Acta Pathol Microbiol Immunol Scand (C) 92S:889–896

    Google Scholar 

  32. Podack ER, Dahlbäck B, Griffin J (1986) Interaction of S-protein of complement with thrombin and antithrombin III during coagulation. J Biol Chem 261:7387–7392

    Google Scholar 

  33. Postlewhaite AE, Keski-Oja J, Moses HL, Kang AH (1987) Stimulation of the chemotactic migration of human fibroblasts by transgrowing growth factor beta. J Exp Med 165:251–256

    Google Scholar 

  34. Pytela R, Pierschbacher MD, Ruoslahti E (1985) A 125/115 kD cell surface receptor specific for vitronectin interacts with the arginine-glycine-aspartic acid adhesion sequence derived from fibronectin. Proc Natl Acad Sci USA 82:5766–5770

    Google Scholar 

  35. Pytela R, Pierschbacher MD, Ginsberg MH, Plow EF, Ruoslahti E (1986) Platelet membrane glycoprotein IIb/IIIa: member of a family of Arg-Gly-Asp-specific adhesion receptors. Science 231:1559–1562

    Google Scholar 

  36. Rapraeger A, Bernfield M (1985) Cell surface proteoglycan of mouse mammary epithelial cells: protease releases a heparan sulfate-rich ectodomain from a putative membrane-anchored domain. J Biol Chem 260:4103–4109

    Google Scholar 

  37. Roberts AB, Sporn MB, Assoain RK, Smith JM, Roche NS, Wakefield LM, Heine UI, Liotta LA, Falanga V, Kehrl JH, Fauci AS (1986) Transgrowing growth factor type-beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci USA 83:4167–4171

    Google Scholar 

  38. Ruoslahti E, Pierschbacher MD (1987) New perspectives in cell adhesion: RGD and integrins. Science 238:491–497

    Google Scholar 

  39. Sheppard D, Rozzo C, Starr L, Quaranta V, Erie DJ, Pytela R (1990) Complete amino acid sequence of a novel integrin β subunit (β6) identified in epithelial cells using the polymerase chain reaction. J Biol Chem 265:11502–11507

    Google Scholar 

  40. Smith JW, Vestal DJ, Irwin SV, Burke TA, Cheresh DA (1990) Purification and functional characterization of integrin αvβ5. An adhesion receptor for vitronectin. J Biol Chem 265:11008–11013

    Google Scholar 

  41. Sporn MB, Roberts AB, Wakefield LM, Crombrugghe B de (1987) Some recent advances in the chemistry and biology of transgrowing growth factor-β. J Cell Biol 105:1039–1045

    Google Scholar 

  42. Stepp MA, Park CC, Spurr-Michaud C, Gipson I (1990) Identification of integrins in stationary and migrating rat corneal epithelia. ARVO Abstracts. Invest Ophthalmol Vis Sci 31:538

    Google Scholar 

  43. Suzuki S, Naitch Y (1990) Amino acid sequence of a novel integrin β4 subunit and primary expression of the mRNA in epithelial cells. EMBO J 9:757–763

    Google Scholar 

  44. Suzuki S, Argraves WS, Arai H, Languino LR, Pierschbacher MD, Ruoslahti E (1987) Amino acid sequence of the vitronectin receptor α subunit and comparative expression of adhesion receptor mRNAs. J Biol Chem 262:14080–14085

    Google Scholar 

  45. Suzuki S, Argraves WS, Pytela R, Arai H, Kruisius T, Pierschbacher MD, Ruoslahti E (1986) cDNA and amino acid sequences of the cell adhesion protein receptor recognising vitronectin reveal a transmembrane domain and homologies with other adhesion protein receptors. Proc Natl Acad Sci USA 83:8614–8618

    Google Scholar 

  46. Vogel BE, Tarone G, Giancotti FG, Gailit J, Ruoslahti E (1990) A novel fibronectin receptor with an unexpected subunit composition (αvβ1). J Biol Chem 265:5934–5937

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Laboratory of Histochemistry and Cytochemistry, Catholic University of Leuven U.Z. St. Rafaël, Kapucijnenvoer 33, B-3000, Leuven, Belgium

    Brigitte Lauweryns & Luc Missotten

  2. Department of Pathology, Laboratory of Histochemistry and Cytochemistry, Catholic University of Leuven U.Z. St. Rafaël, Kapucijnenvoer 33, B-3000, Leuven, Belgium

    Joost J. van den Oord

Authors
  1. Brigitte Lauweryns
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joost J. van den Oord
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Luc Missotten
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Offprint requests to: B. Lauweryns

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lauweryns, B., van den Oord, J.J. & Missotten, L. Localization of the cytoadhesin integrins in the human cornea. Graefe's Arch Clin Exp Ophthalmol 230, 264–268 (1992). https://doi.org/10.1007/BF00176302

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00176302

Keywords

Search

Navigation