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. 1991 Aug 2;114(4):855–863. doi: 10.1083/jcb.114.4.855

Differential distribution and modulation of expression of alpha 1/beta 1 integrin on human endothelial cells

PMCID: PMC2289904  PMID: 1869591

Abstract

In this paper we report that the integrin complex alpha 1/beta 1, a laminin/collagen receptor, is expressed on cultured foreskin microvascular endothelium, but is absent on endothelial cells from large vessels such as the aorta and umbilical and femoral veins. The restricted expression of integrin alpha 1/beta 1 to microvascular endothelium was also demonstrated in vivo, by immunohistochemical staining of human tissue sections. Alpha 1 specific antibodies reacted strongly with endothelial cells of small blood vessels and capillaries in several tissues, but not with endothelium of vein and arteries of umbilical cord. Expression of integrin alpha 1 can be induced in cultured umbilical vein endothelial cells by treatment with 5 ng/ml tumor necrosis factor alpha (TNF alpha). Induction of alpha 1 subunit expression also occurred after treatment of umbilical vein endothelium with 10(-5) M retinoic acid or with 10 nM PMA; Maximal induction of alpha 1 integrin was reached after 48 h of treatment and costimulation with TNF alpha and PMA resulted in a synergistic effect. The induction of alpha 1 integrin changed the adhesive properties of umbilical vein endothelial cells, by increasing the adhesiveness to collagen, laminin, and laminin fragment P1, while adhesion to fibronectin and laminin fragment E8 remained constant. The alpha 1 integrin is thus a marker of a specific population of endothelial cells and its expression confers distinctive properties of interaction with the underlying basal membrane.

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Selected References

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  1. Adams J. C., Gullick W. J. Differences in phorbol-ester-induced down-regulation of protein kinase C between cell lines. Biochem J. 1989 Feb 1;257(3):905–911. doi: 10.1042/bj2570905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Albelda S. M., Daise M., Levine E. M., Buck C. A. Identification and characterization of cell-substratum adhesion receptors on cultured human endothelial cells. J Clin Invest. 1989 Jun;83(6):1992–2002. doi: 10.1172/JCI114109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bevilacqua M. P., Pober J. S., Mendrick D. L., Cotran R. S., Gimbrone M. A., Jr Identification of an inducible endothelial-leukocyte adhesion molecule. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9238–9242. doi: 10.1073/pnas.84.24.9238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brockes J. P. Retinoids, homeobox genes, and limb morphogenesis. Neuron. 1989 Apr;2(4):1285–1294. doi: 10.1016/0896-6273(89)90066-4. [DOI] [PubMed] [Google Scholar]
  5. Castagna M., Takai Y., Kaibuchi K., Sano K., Kikkawa U., Nishizuka Y. Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J Biol Chem. 1982 Jul 10;257(13):7847–7851. [PubMed] [Google Scholar]
  6. Chamberlain J. P. Fluorographic detection of radioactivity in polyacrylamide gels with the water-soluble fluor, sodium salicylate. Anal Biochem. 1979 Sep 15;98(1):132–135. doi: 10.1016/0003-2697(79)90716-4. [DOI] [PubMed] [Google Scholar]
  7. Charo I. F., Bekeart L. S., Phillips D. R. Platelet glycoprotein IIb-IIIa-like proteins mediate endothelial cell attachment to adhesive proteins and the extracellular matrix. J Biol Chem. 1987 Jul 25;262(21):9935–9938. [PubMed] [Google Scholar]
  8. Cheng Y. F., Kramer R. H. Human microvascular endothelial cells express integrin-related complexes that mediate adhesion to the extracellular matrix. J Cell Physiol. 1989 May;139(2):275–286. doi: 10.1002/jcp.1041390209. [DOI] [PubMed] [Google Scholar]
  9. Cheresh D. A. Human endothelial cells synthesize and express an Arg-Gly-Asp-directed adhesion receptor involved in attachment to fibrinogen and von Willebrand factor. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6471–6475. doi: 10.1073/pnas.84.18.6471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Collins T., Lapierre L. A., Fiers W., Strominger J. L., Pober J. S. Recombinant human tumor necrosis factor increases mRNA levels and surface expression of HLA-A,B antigens in vascular endothelial cells and dermal fibroblasts in vitro. Proc Natl Acad Sci U S A. 1986 Jan;83(2):446–450. doi: 10.1073/pnas.83.2.446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Conforti G., Zanetti A., Colella S., Abbadini M., Marchisio P. C., Pytela R., Giancotti F., Tarone G., Languino L. R., Dejana E. Interaction of fibronectin with cultured human endothelial cells: characterization of the specific receptor. Blood. 1989 May 1;73(6):1576–1585. [PubMed] [Google Scholar]
  12. Connolly D. T., Knight M. B., Harakas N. K., Wittwer A. J., Feder J. Determination of the number of endothelial cells in culture using an acid phosphatase assay. Anal Biochem. 1986 Jan;152(1):136–140. doi: 10.1016/0003-2697(86)90131-4. [DOI] [PubMed] [Google Scholar]
  13. Davison P. M., Bensch K., Karasek M. A. Isolation and growth of endothelial cells from the microvessels of the newborn human foreskin in cell culture. J Invest Dermatol. 1980 Oct;75(4):316–321. doi: 10.1111/1523-1747.ep12530941. [DOI] [PubMed] [Google Scholar]
  14. Defilippi P., Truffa G., Stefanuto G., Altruda F., Silengo L., Tarone G. Tumor necrosis factor alpha and interferon gamma modulate the expression of the vitronectin receptor (integrin beta 3) in human endothelial cells. J Biol Chem. 1991 Apr 25;266(12):7638–7645. [PubMed] [Google Scholar]
  15. Dejana E., Languino L. R., Colella S., Corbascio G. C., Plow E., Ginsberg M., Marchisio P. C. The localization of a platelet GpIIb-IIIa-related protein in endothelial cell adhesion structures. Blood. 1988 Mar;71(3):566–572. [PubMed] [Google Scholar]
  16. Edgar D., Timpl R., Thoenen H. Structural requirements for the stimulation of neurite outgrowth by two variants of laminin and their inhibition by antibodies. J Cell Biol. 1988 Apr;106(4):1299–1306. doi: 10.1083/jcb.106.4.1299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Elices M. J., Hemler M. E. The human integrin VLA-2 is a collagen receptor on some cells and a collagen/laminin receptor on others. Proc Natl Acad Sci U S A. 1989 Dec;86(24):9906–9910. doi: 10.1073/pnas.86.24.9906. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Engvall E., Ruoslahti E. Binding of soluble form of fibroblast surface protein, fibronectin, to collagen. Int J Cancer. 1977 Jul 15;20(1):1–5. doi: 10.1002/ijc.2910200102. [DOI] [PubMed] [Google Scholar]
  19. Gehlsen K. R., Dickerson K., Argraves W. S., Engvall E., Ruoslahti E. Subunit structure of a laminin-binding integrin and localization of its binding site on laminin. J Biol Chem. 1989 Nov 15;264(32):19034–19038. [PubMed] [Google Scholar]
  20. Gimbrone M. A., Jr Culture of vascular endothelium. Prog Hemost Thromb. 1976;3:1–28. [PubMed] [Google Scholar]
  21. Hall D. E., Reichardt L. F., Crowley E., Holley B., Moezzi H., Sonnenberg A., Damsky C. H. The alpha 1/beta 1 and alpha 6/beta 1 integrin heterodimers mediate cell attachment to distinct sites on laminin. J Cell Biol. 1990 Jun;110(6):2175–2184. doi: 10.1083/jcb.110.6.2175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Heino J., Ignotz R. A., Hemler M. E., Crouse C., Massagué J. Regulation of cell adhesion receptors by transforming growth factor-beta. Concomitant regulation of integrins that share a common beta 1 subunit. J Biol Chem. 1989 Jan 5;264(1):380–388. [PubMed] [Google Scholar]
  23. Hemler M. E. VLA proteins in the integrin family: structures, functions, and their role on leukocytes. Annu Rev Immunol. 1990;8:365–400. doi: 10.1146/annurev.iy.08.040190.002053. [DOI] [PubMed] [Google Scholar]
  24. Hunter D. D., Shah V., Merlie J. P., Sanes J. R. A laminin-like adhesive protein concentrated in the synaptic cleft of the neuromuscular junction. Nature. 1989 Mar 16;338(6212):229–234. doi: 10.1038/338229a0. [DOI] [PubMed] [Google Scholar]
  25. Hynes R. O. Integrins: a family of cell surface receptors. Cell. 1987 Feb 27;48(4):549–554. doi: 10.1016/0092-8674(87)90233-9. [DOI] [PubMed] [Google Scholar]
  26. Ignatius M. J., Reichardt L. F. Identification of a neuronal laminin receptor: an Mr 200K/120K integrin heterodimer that binds laminin in a divalent cation-dependent manner. Neuron. 1988 Oct;1(8):713–725. doi: 10.1016/0896-6273(88)90170-5. [DOI] [PubMed] [Google Scholar]
  27. Johnson S. E., Baglioni C. Positive and negative regulation of a tumor necrosis factor response in melanoma cells. J Biol Chem. 1990 Apr 25;265(12):6642–6649. [PubMed] [Google Scholar]
  28. Konter U., Kellner I., Klein E., Kaufmann R., Mielke V., Sterry W. Adhesion molecule mapping in normal human skin. Arch Dermatol Res. 1989;281(7):454–462. doi: 10.1007/BF00510080. [DOI] [PubMed] [Google Scholar]
  29. Korhonen M., Ylänne J., Laitinen L., Virtanen I. The alpha 1-alpha 6 subunits of integrins are characteristically expressed in distinct segments of developing and adult human nephron. J Cell Biol. 1990 Sep;111(3):1245–1254. doi: 10.1083/jcb.111.3.1245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Kramer R. H., Cheng Y. F., Clyman R. Human microvascular endothelial cells use beta 1 and beta 3 integrin receptor complexes to attach to laminin. J Cell Biol. 1990 Sep;111(3):1233–1243. doi: 10.1083/jcb.111.3.1233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Kramer R. H., Marks N. Identification of integrin collagen receptors on human melanoma cells. J Biol Chem. 1989 Mar 15;264(8):4684–4688. [PubMed] [Google Scholar]
  32. Languino L. R., Gehlsen K. R., Wayner E., Carter W. G., Engvall E., Ruoslahti E. Endothelial cells use alpha 2 beta 1 integrin as a laminin receptor. J Cell Biol. 1989 Nov;109(5):2455–2462. doi: 10.1083/jcb.109.5.2455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Lapierre L. A., Fiers W., Pober J. S. Three distinct classes of regulatory cytokines control endothelial cell MHC antigen expression. Interactions with immune gamma interferon differentiate the effects of tumor necrosis factor and lymphotoxin from those of leukocyte alpha and fibroblast beta interferons. J Exp Med. 1988 Mar 1;167(3):794–804. doi: 10.1084/jem.167.3.794. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Leibovich S. J., Polverini P. J., Shepard H. M., Wiseman D. M., Shively V., Nuseir N. Macrophage-induced angiogenesis is mediated by tumour necrosis factor-alpha. Nature. 1987 Oct 15;329(6140):630–632. doi: 10.1038/329630a0. [DOI] [PubMed] [Google Scholar]
  35. Leivo I., Engvall E. Merosin, a protein specific for basement membranes of Schwann cells, striated muscle, and trophoblast, is expressed late in nerve and muscle development. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1544–1548. doi: 10.1073/pnas.85.5.1544. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. McGeer P. L., Zhu S. G., Dedhar S. Immunostaining of human brain capillaries by antibodies to very late antigens. J Neuroimmunol. 1990 Mar;26(3):213–218. doi: 10.1016/0165-5728(90)90003-6. [DOI] [PubMed] [Google Scholar]
  37. Montesano R., Orci L. Phorbol esters induce angiogenesis in vitro from large-vessel endothelial cells. J Cell Physiol. 1987 Feb;130(2):284–291. doi: 10.1002/jcp.1041300215. [DOI] [PubMed] [Google Scholar]
  38. Nishizuka Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature. 1984 Apr 19;308(5961):693–698. doi: 10.1038/308693a0. [DOI] [PubMed] [Google Scholar]
  39. Osborn L., Hession C., Tizard R., Vassallo C., Luhowskyj S., Chi-Rosso G., Lobb R. Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes. Cell. 1989 Dec 22;59(6):1203–1211. doi: 10.1016/0092-8674(89)90775-7. [DOI] [PubMed] [Google Scholar]
  40. Pober J. S., Gimbrone M. A., Jr, Lapierre L. A., Mendrick D. L., Fiers W., Rothlein R., Springer T. A. Overlapping patterns of activation of human endothelial cells by interleukin 1, tumor necrosis factor, and immune interferon. J Immunol. 1986 Sep 15;137(6):1893–1896. [PubMed] [Google Scholar]
  41. Pober J. S. Warner-Lambert/Parke-Davis award lecture. Cytokine-mediated activation of vascular endothelium. Physiology and pathology. Am J Pathol. 1988 Dec;133(3):426–433. [PMC free article] [PubMed] [Google Scholar]
  42. Pytela R., Pierschbacher M. D., Ruoslahti E. Identification and isolation of a 140 kd cell surface glycoprotein with properties expected of a fibronectin receptor. Cell. 1985 Jan;40(1):191–198. doi: 10.1016/0092-8674(85)90322-8. [DOI] [PubMed] [Google Scholar]
  43. Rossino P., Gavazzi I., Timpl R., Aumailley M., Abbadini M., Giancotti F., Silengo L., Marchisio P. C., Tarone G. Nerve growth factor induces increased expression of a laminin-binding integrin in rat pheochromocytoma PC12 cells. Exp Cell Res. 1990 Jul;189(1):100–108. doi: 10.1016/0014-4827(90)90262-9. [DOI] [PubMed] [Google Scholar]
  44. Ruoslahti E., Pierschbacher M. D. New perspectives in cell adhesion: RGD and integrins. Science. 1987 Oct 23;238(4826):491–497. doi: 10.1126/science.2821619. [DOI] [PubMed] [Google Scholar]
  45. Santoro S. A., Rajpara S. M., Staatz W. D., Woods V. L., Jr Isolation and characterization of a platelet surface collagen binding complex related to VLA-2. Biochem Biophys Res Commun. 1988 May 31;153(1):217–223. doi: 10.1016/s0006-291x(88)81211-7. [DOI] [PubMed] [Google Scholar]
  46. Schütze S., Nottrott S., Pfizenmaier K., Krönke M. Tumor necrosis factor signal transduction. Cell-type-specific activation and translocation of protein kinase C. J Immunol. 1990 Apr 1;144(7):2604–2608. [PubMed] [Google Scholar]
  47. Sonnenberg A., Linders C. J., Modderman P. W., Damsky C. H., Aumailley M., Timpl R. Integrin recognition of different cell-binding fragments of laminin (P1, E3, E8) and evidence that alpha 6 beta 1 but not alpha 6 beta 4 functions as a major receptor for fragment E8. J Cell Biol. 1990 Jun;110(6):2145–2155. doi: 10.1083/jcb.110.6.2145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Sonnenberg A., Modderman P. W., Hogervorst F. Laminin receptor on platelets is the integrin VLA-6. Nature. 1988 Dec 1;336(6198):487–489. doi: 10.1038/336487a0. [DOI] [PubMed] [Google Scholar]
  49. Staatz W. D., Rajpara S. M., Wayner E. A., Carter W. G., Santoro S. A. The membrane glycoprotein Ia-IIa (VLA-2) complex mediates the Mg++-dependent adhesion of platelets to collagen. J Cell Biol. 1989 May;108(5):1917–1924. doi: 10.1083/jcb.108.5.1917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Sternberger L. A., Hardy P. H., Jr, Cuculis J. J., Meyer H. G. The unlabeled antibody enzyme method of immunohistochemistry: preparation and properties of soluble antigen-antibody complex (horseradish peroxidase-antihorseradish peroxidase) and its use in identification of spirochetes. J Histochem Cytochem. 1970 May;18(5):315–333. doi: 10.1177/18.5.315. [DOI] [PubMed] [Google Scholar]
  51. Tarone G., Galetto G., Prat M., Comoglio P. M. Cell surface molecules and fibronectin-mediated cell adhesion: effect of proteolytic digestion of membrane proteins. J Cell Biol. 1982 Jul;94(1):179–186. doi: 10.1083/jcb.94.1.179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Tarone G., Stefanuto G., Mascarello P., Defilippi P., Altruda F., Silengo L. Expression of receptors for extracellular matrix proteins in human endothelial cells. J Lipid Mediat. 1990;2 (Suppl):S45–S53. [PubMed] [Google Scholar]
  53. Turner D. C., Flier L. A., Carbonetto S. Identification of a cell-surface protein involved in PC12 cell-substratum adhesion and neurite outgrowth on laminin and collagen. J Neurosci. 1989 Sep;9(9):3287–3296. doi: 10.1523/JNEUROSCI.09-09-03287.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Van Hinsbergh V. W., Sprengers E. D., Kooistra T. Effect of thrombin on the production of plasminogen activators and PA inhibitor-1 by human foreskin microvascular endothelial cells. Thromb Haemost. 1987 Apr 7;57(2):148–153. [PubMed] [Google Scholar]
  55. Voyta J. C., Via D. P., Butterfield C. E., Zetter B. R. Identification and isolation of endothelial cells based on their increased uptake of acetylated-low density lipoprotein. J Cell Biol. 1984 Dec;99(6):2034–2040. doi: 10.1083/jcb.99.6.2034. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. van Hinsbergh V. W., Binnema D., Scheffer M. A., Sprengers E. D., Kooistra T., Rijken D. C. Production of plasminogen activators and inhibitor by serially propagated endothelial cells from adult human blood vessels. Arteriosclerosis. 1987 Jul-Aug;7(4):389–400. doi: 10.1161/01.atv.7.4.389. [DOI] [PubMed] [Google Scholar]

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