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. 1994 Nov 2;127(4):1129–1137. doi: 10.1083/jcb.127.4.1129

Integrin alpha v beta 3 differentially regulates adhesive and phagocytic functions of the fibronectin receptor alpha 5 beta 1

PMCID: PMC2200054  PMID: 7525603

Abstract

The plasma protein fibronectin is an important opsonin in wound repair and host defense. To better understand the process of fibronectin- mediated phagocytosis, we have transfected K562 cells, which endogenously express alpha 5 beta 1, with alpha v beta 3. In these transfectants, antibodies to alpha v beta 3 block phagocytosis of fibronectin-opsonized beads completely, even though half the ingestion occurs through endogenous alpha 5 beta 1 receptors. alpha 5 beta 1- mediated adhesion to fibronectin-coated surfaces is unaffected by alpha v beta 3 ligation. Neither alpha v beta 5 nor alpha M beta 2 ligation affects alpha 5 beta 1 phagocytic function in transfectants expressing these receptors. Pharmacologic data suggest that alpha v beta 3 ligation suppresses the phagocytic competence of high affinity alpha 5 beta 1 receptors through a signal transduction pathway, perhaps involving protein kinase C. In addition to its significance for phagocytosis, alpha v beta 3 regulation of alpha 5 beta 1 function may be significant for its roles in cell migration, metastasis, and angiogenesis.

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Selected References

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  1. Altieri D. C., Bader R., Mannucci P. M., Edgington T. S. Oligospecificity of the cellular adhesion receptor Mac-1 encompasses an inducible recognition specificity for fibrinogen. J Cell Biol. 1988 Nov;107(5):1893–1900. doi: 10.1083/jcb.107.5.1893. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Altieri D. C., Wiltse W. L., Edgington T. S. Signal transduction initiated by extracellular nucleotides regulates the high affinity ligand recognition of the adhesive receptor CD11b/CD18. J Immunol. 1990 Jul 15;145(2):662–670. [PubMed] [Google Scholar]
  3. Andoh A., Fujiyama Y., Kitoh K., Hodohara K., Bamba T., Hosoda S. Flow cytometric assay for phagocytosis of human monocytes mediated via Fc gamma-receptors and complement receptor CR1 (CD35). Cytometry. 1991;12(7):677–686. doi: 10.1002/cyto.990120712. [DOI] [PubMed] [Google Scholar]
  4. Arroyo A. G., García-Pardo A., Sánchez-Madrid F. A high affinity conformational state on VLA integrin heterodimers induced by an anti-beta 1 chain monoclonal antibody. J Biol Chem. 1993 May 5;268(13):9863–9868. [PubMed] [Google Scholar]
  5. Arroyo A. G., Sánchez-Mateos P., Campanero M. R., Martín-Padura I., Dejana E., Sánchez-Madrid F. Regulation of the VLA integrin-ligand interactions through the beta 1 subunit. J Cell Biol. 1992 May;117(3):659–670. doi: 10.1083/jcb.117.3.659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Barnstable C. J., Bodmer W. F., Brown G., Galfre G., Milstein C., Williams A. F., Ziegler A. Production of monoclonal antibodies to group A erythrocytes, HLA and other human cell surface antigens-new tools for genetic analysis. Cell. 1978 May;14(1):9–20. doi: 10.1016/0092-8674(78)90296-9. [DOI] [PubMed] [Google Scholar]
  7. Beezhold D. H., Lause D. B. Stimulation of rat macrophage interleukin 1 secretion by plasma fibronectin. Immunol Invest. 1987 Aug;16(5):437–449. doi: 10.3109/08820138709087097. [DOI] [PubMed] [Google Scholar]
  8. Bevilacqua M. P., Amrani D., Mosesson M. W., Bianco C. Receptors for cold-insoluble globulin (plasma fibronectin) on human monocytes. J Exp Med. 1981 Jan 1;153(1):42–60. doi: 10.1084/jem.153.1.42. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Blystone S. D., Kaplan J. E. Isolation of an amino-terminal fibronectin-binding protein on human U937 cells and rat peritoneal macrophages. J Biol Chem. 1992 Feb 25;267(6):3968–3975. [PubMed] [Google Scholar]
  10. Blystone S. D., Weston L. K., Kaplan J. E. Fibronectin dependent macrophage fibrin binding. Blood. 1991 Dec 1;78(11):2900–2907. [PubMed] [Google Scholar]
  11. Bohnsack J. F., Takahashi T., Brown E. J. Interaction of culture-derived macrophages with the fibroblast-binding domain of fibronectin is a necessary but inefficient signal for fibronectin enhancement of CR1-mediated phagocytosis. J Immunol. 1986 May 15;136(10):3793–3798. [PubMed] [Google Scholar]
  12. Brown E. J., Goodwin J. L. Fibronectin receptors of phagocytes. Characterization of the Arg-Gly-Asp binding proteins of human monocytes and polymorphonuclear leukocytes. J Exp Med. 1988 Mar 1;167(3):777–793. doi: 10.1084/jem.167.3.777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Carter W. G., Ryan M. C., Gahr P. J. Epiligrin, a new cell adhesion ligand for integrin alpha 3 beta 1 in epithelial basement membranes. Cell. 1991 May 17;65(4):599–610. doi: 10.1016/0092-8674(91)90092-d. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Cheresh D. A., Smith J. W., Cooper H. M., Quaranta V. A novel vitronectin receptor integrin (alpha v beta x) is responsible for distinct adhesive properties of carcinoma cells. Cell. 1989 Apr 7;57(1):59–69. doi: 10.1016/0092-8674(89)90172-4. [DOI] [PubMed] [Google Scholar]
  16. Cheresh D. A., Spiro R. C. 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. 1987 Dec 25;262(36):17703–17711. [PubMed] [Google Scholar]
  17. Cobb B. S., Schaller M. D., Leu T. H., Parsons J. T. Stable association of pp60src and pp59fyn with the focal adhesion-associated protein tyrosine kinase, pp125FAK. Mol Cell Biol. 1994 Jan;14(1):147–155. doi: 10.1128/mcb.14.1.147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Conforti G., Dominguez-Jimenez C., Zanetti A., Gimbrone M. A., Jr, Cremona O., Marchisio P. C., Dejana E. Human endothelial cells express integrin receptors on the luminal aspect of their membrane. Blood. 1992 Jul 15;80(2):437–446. [PubMed] [Google Scholar]
  19. Darribère T., Guida K., Larjava H., Johnson K. E., Yamada K. M., Thiery J. P., Boucaut J. C. In vivo analyses of integrin beta 1 subunit function in fibronectin matrix assembly. J Cell Biol. 1990 May;110(5):1813–1823. doi: 10.1083/jcb.110.5.1813. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Davis C. M., Danehower S. C., Laurenza A., Molony J. L. Identification of a role of the vitronectin receptor and protein kinase C in the induction of endothelial cell vascular formation. J Cell Biochem. 1993 Feb;51(2):206–218. doi: 10.1002/jcb.240510213. [DOI] [PubMed] [Google Scholar]
  21. De Nichilo M. O., Burns G. F. Granulocyte-macrophage and macrophage colony-stimulating factors differentially regulate alpha v integrin expression on cultured human macrophages. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2517–2521. doi: 10.1073/pnas.90.6.2517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Deno D. C., McCafferty M. H., Saba T. M., Blumenstock F. A. Mechanism of acute depletion of plasma fibronectin following thermal injury in rats. Appearance of a gelatinlike ligand in plasma. J Clin Invest. 1984 Jan;73(1):20–34. doi: 10.1172/JCI111191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Detmers P. A., Wright S. D., Olsen E., Kimball B., Cohn Z. A. Aggregation of complement receptors on human neutrophils in the absence of ligand. J Cell Biol. 1987 Sep;105(3):1137–1145. doi: 10.1083/jcb.105.3.1137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Doherty D. E., Henson P. M., Clark R. A. Fibronectin fragments containing the RGDS cell-binding domain mediate monocyte migration into the rabbit lung. A potential mechanism for C5 fragment-induced monocyte lung accumulation. J Clin Invest. 1990 Oct;86(4):1065–1075. doi: 10.1172/JCI114809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Faull R. J., Kovach N. L., Harlan J. M., Ginsberg M. H. Affinity modulation of integrin alpha 5 beta 1: regulation of the functional response by soluble fibronectin. J Cell Biol. 1993 Apr;121(1):155–162. doi: 10.1083/jcb.121.1.155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Felding-Habermann B., Mueller B. M., Romerdahl C. A., Cheresh D. A. Involvement of integrin alpha V gene expression in human melanoma tumorigenicity. J Clin Invest. 1992 Jun;89(6):2018–2022. doi: 10.1172/JCI115811. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Ferreira O. C., Jr, Garcia-Pardo A., Bianco C. Specific binding of the human monocytic cell line U937 to the alternatively spliced connecting segment (IIICS) of fibronectin. J Exp Med. 1990 Jan 1;171(1):351–356. doi: 10.1084/jem.171.1.351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Ferreira O. C., Jr, Valinsky J. E., Sheridan K., Wayner E. A., Bianco C., Garcia-Pardo A. Phorbol ester-induced differentiation of U937 cells enhances attachment to fibronectin and distinctly modulates the alpha 5 beta 1 and alpha 4 beta 1 fibronectin receptors. Exp Cell Res. 1991 Mar;193(1):20–26. doi: 10.1016/0014-4827(91)90533-z. [DOI] [PubMed] [Google Scholar]
  29. Greenberg S., el Khoury J., Kaplan E., Silverstein S. C. A fluorescence technique to distinguish attached from ingested erythrocytes and zymosan particles in phagocytosing macrophages. J Immunol Methods. 1991 May 17;139(1):115–122. doi: 10.1016/0022-1759(91)90358-m. [DOI] [PubMed] [Google Scholar]
  30. Gresham H. D., Goodwin J. L., Allen P. M., Anderson D. C., Brown E. J. A novel member of the integrin receptor family mediates Arg-Gly-Asp-stimulated neutrophil phagocytosis. J Cell Biol. 1989 May;108(5):1935–1943. doi: 10.1083/jcb.108.5.1935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Grinnell F. Fibroblast receptor for cell-substratum adhesion: studies on the interaction of baby hamster kidney cells with latex beads coated by cold insoluble globulin (plasma fibronectin). J Cell Biol. 1980 Jul;86(1):104–112. doi: 10.1083/jcb.86.1.104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. 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]
  33. Hemler M. E., Sanchez-Madrid F., Flotte T. J., Krensky A. M., Burakoff S. J., Bhan A. K., Springer T. A., Strominger J. L. Glycoproteins of 210,000 and 130,000 m.w. on activated T cells: cell distribution and antigenic relation to components on resting cells and T cell lines. J Immunol. 1984 Jun;132(6):3011–3018. [PubMed] [Google Scholar]
  34. Hidaka H., Inagaki M., Kawamoto S., Sasaki Y. Isoquinolinesulfonamides, novel and potent inhibitors of cyclic nucleotide dependent protein kinase and protein kinase C. Biochemistry. 1984 Oct 9;23(21):5036–5041. doi: 10.1021/bi00316a032. [DOI] [PubMed] [Google Scholar]
  35. Kirchhofer D., Gailit J., Ruoslahti E., Grzesiak J., Pierschbacher M. D. Cation-dependent changes in the binding specificity of the platelet receptor GPIIb/IIIa. J Biol Chem. 1990 Oct 25;265(30):18525–18530. [PubMed] [Google Scholar]
  36. Kobayashi E., Nakano H., Morimoto M., Tamaoki T. Calphostin C (UCN-1028C), a novel microbial compound, is a highly potent and specific inhibitor of protein kinase C. Biochem Biophys Res Commun. 1989 Mar 15;159(2):548–553. doi: 10.1016/0006-291x(89)90028-4. [DOI] [PubMed] [Google Scholar]
  37. Kornberg L. J., Earp H. S., Turner C. E., Prockop C., Juliano R. L. Signal transduction by integrins: increased protein tyrosine phosphorylation caused by clustering of beta 1 integrins. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8392–8396. doi: 10.1073/pnas.88.19.8392. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Kovach N. L., Carlos T. M., Yee E., Harlan J. M. A monoclonal antibody to beta 1 integrin (CD29) stimulates VLA-dependent adherence of leukocytes to human umbilical vein endothelial cells and matrix components. J Cell Biol. 1992 Jan;116(2):499–509. doi: 10.1083/jcb.116.2.499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Kowalczyk A. P., Tulloh R. H., McKeown-Longo P. J. Polarized fibronectin secretion and localized matrix assembly sites correlate with subendothelial matrix formation. Blood. 1990 Jun 15;75(12):2335–2342. [PubMed] [Google Scholar]
  40. La Celle P., Blumenstock F. A., McKinley C., Saba T. M., Vincent P. A., Gray V. Blood-borne collagenous debris complexes with plasma fibronectin after thermal injury. Blood. 1990 Jan 15;75(2):470–478. [PubMed] [Google Scholar]
  41. Leavesley D. I., Ferguson G. D., Wayner E. A., Cheresh D. A. Requirement of the integrin beta 3 subunit for carcinoma cell spreading or migration on vitronectin and fibrinogen. J Cell Biol. 1992 Jun;117(5):1101–1107. doi: 10.1083/jcb.117.5.1101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Lindberg F. P., Gresham H. D., Schwarz E., Brown E. J. Molecular cloning of integrin-associated protein: an immunoglobulin family member with multiple membrane-spanning domains implicated in alpha v beta 3-dependent ligand binding. J Cell Biol. 1993 Oct;123(2):485–496. doi: 10.1083/jcb.123.2.485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Loftus J. C., O'Toole T. E., Plow E. F., Glass A., Frelinger A. L., 3rd, Ginsberg M. H. A beta 3 integrin mutation abolishes ligand binding and alters divalent cation-dependent conformation. Science. 1990 Aug 24;249(4971):915–918. doi: 10.1126/science.2392682. [DOI] [PubMed] [Google Scholar]
  44. Martin B. M., Gimbrone M. A., Jr, Majeau G. R., Unanue E. R., Cotran R. S. Stimulation of human monocyte/macrophage-derived growth factor (MDGF) production by plasma fibronectin. Am J Pathol. 1983 Jun;111(3):367–373. [PMC free article] [PubMed] [Google Scholar]
  45. McLean J. W., Vestal D. J., Cheresh D. A., Bodary S. C. cDNA sequence of the human integrin beta 5 subunit. J Biol Chem. 1990 Oct 5;265(28):17126–17131. [PubMed] [Google Scholar]
  46. Michl J., Pieczonka M. M., Unkeless J. C., Bell G. I., Silverstein S. C. Fc receptor modulation in mononuclear phagocytes maintained on immobilized immune complexes occurs by diffusion of the receptor molecule. J Exp Med. 1983 Jun 1;157(6):2121–2139. doi: 10.1084/jem.157.6.2121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Niehaus G. D., Schumacker P. T., Saba T. M. Influence of opsonic fibronectin deficiency on lung fluid balance during bacterial sepsis. J Appl Physiol Respir Environ Exerc Physiol. 1980 Oct;49(4):693–699. doi: 10.1152/jappl.1980.49.4.693. [DOI] [PubMed] [Google Scholar]
  48. Nip J., Shibata H., Loskutoff D. J., Cheresh D. A., Brodt P. Human melanoma cells derived from lymphatic metastases use integrin alpha v beta 3 to adhere to lymph node vitronectin. J Clin Invest. 1992 Oct;90(4):1406–1413. doi: 10.1172/JCI116007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Norris D. A., Clark R. A., Swigart L. M., Huff J. C., Weston W. L., Howell S. E. Fibronectin fragment(s) are chemotactic for human peripheral blood monocytes. J Immunol. 1982 Oct;129(4):1612–1618. [PubMed] [Google Scholar]
  50. O'Toole T. E., Katagiri Y., Faull R. J., Peter K., Tamura R., Quaranta V., Loftus J. C., Shattil S. J., Ginsberg M. H. Integrin cytoplasmic domains mediate inside-out signal transduction. J Cell Biol. 1994 Mar;124(6):1047–1059. doi: 10.1083/jcb.124.6.1047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Pommier C. G., Inada S., Fries L. F., Takahashi T., Frank M. M., Brown E. J. Plasma fibronectin enhances phagocytosis of opsonized particles by human peripheral blood monocytes. J Exp Med. 1983 Jun 1;157(6):1844–1854. doi: 10.1084/jem.157.6.1844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Saba T. M., Blumenstock F. A., Scovill W. A., Bernard H. Cryoprecipitate reversal of opsonic alpha2-surface binding glycoprotein deficiency in septic surgical and trauma patients. Science. 1978 Aug 18;201(4356):622–624. doi: 10.1126/science.675246. [DOI] [PubMed] [Google Scholar]
  53. Savage B., Ruggeri Z. M. Selective recognition of adhesive sites in surface-bound fibrinogen by glycoprotein IIb-IIIa on nonactivated platelets. J Biol Chem. 1991 Jun 15;266(17):11227–11233. [PubMed] [Google Scholar]
  54. Schaller M. D., Borgman C. A., Cobb B. S., Vines R. R., Reynolds A. B., Parsons J. T. pp125FAK a structurally distinctive protein-tyrosine kinase associated with focal adhesions. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):5192–5196. doi: 10.1073/pnas.89.11.5192. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Schwartz M. A., Denninghoff K. Alpha v integrins mediate the rise in intracellular calcium in endothelial cells on fibronectin even though they play a minor role in adhesion. J Biol Chem. 1994 Apr 15;269(15):11133–11137. [PubMed] [Google Scholar]
  56. Scovill W. A., Saba T. M., Kaplan J. E., Bernard H., Powers S., Jr Deficits in reticuloendothelial humoral control mechanisms in patients after trauma. J Trauma. 1976 Nov;16(11):898–904. doi: 10.1097/00005373-197611000-00008. [DOI] [PubMed] [Google Scholar]
  57. Smith J. W., Vestal D. J., Irwin S. V., Burke T. A., Cheresh D. A. Purification and functional characterization of integrin alpha v beta 5. An adhesion receptor for vitronectin. J Biol Chem. 1990 Jul 5;265(19):11008–11013. [PubMed] [Google Scholar]
  58. Sánchez-Mateos P., Arroyo A. G., Balboa M. A., Sánchez-Madrid F. Post-receptor occupancy events in leukocytes during beta 1 integrin-ligand interactions. Eur J Immunol. 1993 Oct;23(10):2642–2648. doi: 10.1002/eji.1830231038. [DOI] [PubMed] [Google Scholar]
  59. Tang D. G., Grossi I. M., Chen Y. Q., Diglio C. A., Honn K. V. 12(S)-HETE promotes tumor-cell adhesion by increasing surface expression of alpha V beta 3 integrins on endothelial cells. Int J Cancer. 1993 Apr 22;54(1):102–111. doi: 10.1002/ijc.2910540117. [DOI] [PubMed] [Google Scholar]
  60. Van Strijp J. A., Russell D. G., Tuomanen E., Brown E. J., Wright S. D. Ligand specificity of purified complement receptor type three (CD11b/CD18, alpha m beta 2, Mac-1). Indirect effects of an Arg-Gly-Asp (RGD) sequence. J Immunol. 1993 Sep 15;151(6):3324–3336. [PubMed] [Google Scholar]
  61. Wayner E. A., Orlando R. A., Cheresh D. A. Integrins alpha v beta 3 and alpha v beta 5 contribute to cell attachment to vitronectin but differentially distribute on the cell surface. J Cell Biol. 1991 May;113(4):919–929. doi: 10.1083/jcb.113.4.919. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Werb Z., Tremble P. M., Behrendtsen O., Crowley E., Damsky C. H. Signal transduction through the fibronectin receptor induces collagenase and stromelysin gene expression. J Cell Biol. 1989 Aug;109(2):877–889. doi: 10.1083/jcb.109.2.877. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Wright S. D., Craigmyle L. S., Silverstein S. C. Fibronectin and serum amyloid P component stimulate C3b- and C3bi-mediated phagocytosis in cultured human monocytes. J Exp Med. 1983 Oct 1;158(4):1338–1343. doi: 10.1084/jem.158.4.1338. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Wright S. D., Meyer B. C. Phorbol esters cause sequential activation and deactivation of complement receptors on polymorphonuclear leukocytes. J Immunol. 1986 Mar 1;136(5):1759–1764. [PubMed] [Google Scholar]
  65. Wright S. D., Rao P. E., Van Voorhis W. C., Craigmyle L. S., Iida K., Talle M. A., Westberg E. F., Goldstein G., Silverstein S. C. Identification of the C3bi receptor of human monocytes and macrophages by using monoclonal antibodies. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5699–5703. doi: 10.1073/pnas.80.18.5699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Yatohgo T., Izumi M., Kashiwagi H., Hayashi M. Novel purification of vitronectin from human plasma by heparin affinity chromatography. Cell Struct Funct. 1988 Aug;13(4):281–292. doi: 10.1247/csf.13.281. [DOI] [PubMed] [Google Scholar]
  67. Zheleznyak A., Brown E. J. Immunoglobulin-mediated phagocytosis by human monocytes requires protein kinase C activation. Evidence for protein kinase C translocation to phagosomes. J Biol Chem. 1992 Jun 15;267(17):12042–12048. [PubMed] [Google Scholar]

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