Abstract
Purpose Integrins are heterodimeric cell surface molecules involved in cell-cell and cell-matrix interactions. Adenoviral entry into human cells has been shown to be dependent on integrins αvβ5 and αvβ3 that promote viral intemalisation. We studied the distribution of integrins αvβ5, αvβ3 and the αv chain in normal human cornea to investigate possible mechanisms of adenoviral entry to specific corneal cell types.
Methods We used immunohistochemistry with monoclonal antibodies to study the distribution of αvβ5, αvβ3 and αv in normal human corneas maintained for up to 4 days in Corneal storage medium (Optisol) at 4 °C (n = 9).
Results Both αvβ5 and αv were present to a variable extent on the corneal epithelium and Corneal endothelium of most specimens. In some specimens staining of both αvβ5 and αv in the epithelium was graded, with more basal than superficial staining, αvβ3 was not detectable in either the Corneal epithelium or the Corneal endothelium in those specimens tested.
Conclusions The integrin αvβ5 is present on both epithelium and endothelium in the normal human cornea. The role of αv integrins in clinical infection and in adenoviral entry for gene transfer is discussed.
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Loftus JC, Smith JW, Ginsberg MH . Integrin mediated cell adhesion: the extracellular face. J Biol Chem 1994;269:25235–8.
Horton M . Current status review. Vitronectin receptor: tissue specific expression or adaptation to culture? Int J Exp Pathol 1990;70:741–59.
Bosman FT . Integrins: cell adhesives and modulators of cell function. Histochem J 1993;25:469–77.
Smith JW, Vestal DJ, Irwin SV, Burke TA, Cheresh DA . Purification and functional characterisation of integrin αvβ5 . J Biol Chem 1990;265:11008–13.
Wickham TJ, Mathias P, Cheresh DA, Nemerow GR . Integrins αvβ3 and αvβ5 promote adenoviral internalisation but not virus attachment. Cell 1993;73:309–19.
Friedlander M, Brooks PC, Shaffer RW, Kincaid CM, Varner JA, Cheresh DA . Definition of two angiogenic pathways by distinct αv integrins. Science 1995;270:1500–2.
Friedlander M, Theesfeld CL, Sugita M, Fruttiger M, Thomas MA, Chang S, Cheresh DA . Involvement of integrins αvβ3 and αvβ5 in ocular neovascular disease. Proc Natl Acad Sci USA 1996;93:9764–9.
Rowe WP, Huebner RJ, Gillmore LK, Parrott RH, Ward TG . Isolation of a cytopathogenic agent from human adenoids undergoing a spontaneous degeneration in tissue culture. Proc Soc Exp Biol Med 1953;84:570–3.
Nicholson F . Introduction to adenoviruses: an overview of morphology, classification and epidemiology. Eye 1993;7(Suppl):1–4.
Bergelson JM, Cunningham JA, Droguett G, Kurt-Jones EA, Krithivas A, Hong JS, et al. Isolation of a common receptor for coxsackie B viruses and adenoviruses 2 and 5. Science 1997;275:1320–3.
Mathias P, Wickham T, Moore M, Nemerow G . Multiple adenovirus serotypes use αv integrins for infection. J Virol 1994;68:6811–4.
Nemerow GR, Cheresh DA, Wickham TJ . Adenovirus entry into host cells: a role for αv integrins. Trends Cell Biol 1994;4:52–5.
Mashhour B, Coton D, Perricaudet M, Briand P . In vivo adenovirus-mediated gene transfer into ocular tissues. Gene Ther 1994;1:122–6.
Larkin DFP, Oral HB, Ring CJA, Lemoine NR, George AJT . Adenovirus-mediated gene delivery to the corneal endothelium. Transplantation 1996;61:363–70.
Oral HB, Larkin DFP, Fehervari Z, Byrnes AP, Rankin AM, Wood MJA, et al. Ex vivo adenovirus-mediated gene transfer and immunomodulatory protein production in human cornea. Gene Ther 1997;4:639–47.
Fehervari Z, Rayner SA, Oral HB, George AJT, Larkin DFP . Gene transfer to ex vivo stored corneas. Cornea 1997;16:459–64.
Abraham NG, da Silva JL, Lavrovsky Y, Stolz RA, Kappas A, Dunn MW, Schwartzman ML . Adenovirus-mediated heme oxygenase-1 gene transfer into rabbit ocular tissues. Invest Ophthalmol Vis Sci 1995;36:2202–10.
Goldman MJ, Wilson JM . Expression of αvβ5 integrin is necessary for efficient adenovirus-mediated gene transfer in the human airway. J Virol 1995;69:5951–8.
Goldman M, Su Q, Wilson JM . Gradient of RGD-dependent entry of adenoviral vector in nasal and intrapulmonary epithelial implications for gene therapy of cystic fibrosis. Gene Ther 1996;3:811–8.
Tervo K, Tervo T, Van SG, Virtanen I . Integrins in human corneal epithelium. Cornea 1991;10:461–5.
Lauweryns B, van den Oord J, Volpes R, Foets B, Missotten L . Distribution of very late activation integrins in the human cornea. Invest Ophthalmol Vis Sci 1991;32:2079–85.
Lauweryns B, van den Oord J, Missotten L . Localisation of the cytoadhesin integrins in the human cornea. Graefes Arch Clin Exp Ophthalmol 1992;230:264–8.
Vorkauf W, Vorkauf M, Nolle B, Duncker G . Adhesion molecules in normal and pathological corneas. Graefes Arch Clin Exp Ophthalmol 1995;233:209–19.
Stepp MA, Spurr-Michaud S, Gipson IK . Integrins in the wounded and unwounded stratified squamous epithelium of the cornea. Invest Ophthalmol Vis Sci 1993;34:1829–45.
Stepp MJ, Zhu L, Cranfill R . Changes in β4 integrin expression and localisation in vivo in response to corneal epithelial injury. Invest Ophthalmol Vis Sci 1996;37:1593–601.
Latvala T, Paallysaho T, Tervo K, Tervo T . Distribution of α6 and β4 integrins following epithelial abrasion in the rabbit cornea. Acta Ophthalmol Scand 1996;74:21–5.
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This project was supported by a grant from the Ins Fund for Prevention of Blindness to S.A.R.
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Rayner, S., Gallop, J., George, A. et al. Distribution of integrins αvβ5, αvβ3 and αv in normal human cornea: Possible implications in clinical and therapeutic adenoviral infection. Eye 12, 273–277 (1998). https://doi.org/10.1038/eye.1998.63
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DOI: https://doi.org/10.1038/eye.1998.63
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