Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1988 Mar 1;167(3):777–793. doi: 10.1084/jem.167.3.777

Fibronectin receptors of phagocytes. Characterization of the Arg-Gly- Asp binding proteins of human monocytes and polymorphonuclear leukocytes

PMCID: PMC2188897  PMID: 2965209

Abstract

We have defined the cell surface molecules of human monocytes and PMN that bind to the chymotryptic cell binding domain of Fn and to a synthetic peptide, KYAVTGRGDS, based on the sequence of Fn, by affinity chromatography. Monocytes express two receptors that differ in their affinity for CBD-Sepharose and peptide-Sepharose, but that both recognize the RGD sequence. Only a single receptor is purified from PMN, which resembles the monocyte surface molecule that binds to peptide-Sepharose. These receptors are not part of the Mac-1, LFA-1, p(150,95) family, but do have homology to the platelet Fn receptor, gpIIb/IIIa. Interestingly, the antigenic crossreactivity between gpIIb/IIIa and the phagocyte receptors purified on peptide-Sepharose is largely in the beta chain of the receptors. The alpha chains appear to be distinct, based on molecular weight, antigenic analysis, and ligand specificity. This receptor also seems to be the surface molecule on monocytes that is critical for phagocytosis enhancement by Fn. Thus, we have defined the phagocyte Fn receptor that transduces the signal for increased phagocytosis by monocytes; it may be a third member of a family of adhesion molecules that includes the gpIIb/IIIa of platelets and the vitronectin receptor of fibroblasts.

Full Text

The Full Text of this article is available as a PDF (1.1 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akiyama S. K., Yamada S. S., Yamada K. M. Characterization of a 140-kD avian cell surface antigen as a fibronectin-binding molecule. J Cell Biol. 1986 Feb;102(2):442–448. doi: 10.1083/jcb.102.2.442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Allison J. P., McIntyre B. W., Bloch D. Tumor-specific antigen of murine T-lymphoma defined with monoclonal antibody. J Immunol. 1982 Nov;129(5):2293–2300. [PubMed] [Google Scholar]
  3. Berger M., O'Shea J., Cross A. S., Folks T. M., Chused T. M., Brown E. J., Frank M. M. Human neutrophils increase expression of C3bi as well as C3b receptors upon activation. J Clin Invest. 1984 Nov;74(5):1566–1571. doi: 10.1172/JCI111572. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bohnsack J. F., Kleinman H. K., Takahashi T., O'Shea J. J., Brown E. J. Connective tissue proteins and phagocytic cell function. Laminin enhances complement and Fc-mediated phagocytosis by cultured human macrophages. J Exp Med. 1985 May 1;161(5):912–923. doi: 10.1084/jem.161.5.912. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Brown P. J., Juliano R. L. Expression and function of a putative cell surface receptor for fibronectin in hamster and human cell lines. J Cell Biol. 1986 Oct;103(4):1595–1603. doi: 10.1083/jcb.103.4.1595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Burns G. F., Cosgrove L., Triglia T., Beall J. A., López A. F., Werkmeister J. A., Begley C. G., Haddad A. P., d'Apice A. J., Vadas M. A. The IIb-IIIa glycoprotein complex that mediates platelet aggregation is directly implicated in leukocyte adhesion. Cell. 1986 Apr 25;45(2):269–280. doi: 10.1016/0092-8674(86)90391-0. [DOI] [PubMed] [Google Scholar]
  8. Fearon D. T., Collins L. A. Increased expression of C3b receptors on polymorphonuclear leukocytes induced by chemotactic factors and by purification procedures. J Immunol. 1983 Jan;130(1):370–375. [PubMed] [Google Scholar]
  9. Gartner T. K., Bennett J. S. The tetrapeptide analogue of the cell attachment site of fibronectin inhibits platelet aggregation and fibrinogen binding to activated platelets. J Biol Chem. 1985 Oct 5;260(22):11891–11894. [PubMed] [Google Scholar]
  10. Ginsberg M. H., Lightsey A., Kunicki T. J., Kaufmann A., Marguerie G., Plow E. F. Divalent cation regulation of the surface orientation of platelet membrane glycoprotein IIb. Correlation with fibrinogen binding function and definition of a novel variant of Glanzmann's thrombasthenia. J Clin Invest. 1986 Oct;78(4):1103–1111. doi: 10.1172/JCI112667. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ginsberg M. H., Loftus J., Ryckwaert J. J., Pierschbacher M., Pytela R., Ruoslahti E., Plow E. F. Immunochemical and amino-terminal sequence comparison of two cytoadhesins indicates they contain similar or identical beta subunits and distinct alpha subunits. J Biol Chem. 1987 Apr 25;262(12):5437–5440. [PubMed] [Google Scholar]
  12. Gresham H. D., Clement L. T., Lehmeyer J. E., Griffin F. M., Jr, Volanakis J. E. Stimulation of human neutrophil Fc receptor-mediated phagocytosis by a low molecular weight cytokine. J Immunol. 1986 Aug 1;137(3):868–875. [PubMed] [Google Scholar]
  13. Griffin J. A., Griffin F. M., Jr Augmentation of macrophage complement receptor function in vitro. I. Characterization of the cellular interactions required for the generation of a T-lymphocyte product that enhances macrophage complement receptor function. J Exp Med. 1979 Sep 19;150(3):653–675. doi: 10.1084/jem.150.3.653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Horwitz A., Duggan K., Greggs R., Decker C., Buck C. The cell substrate attachment (CSAT) antigen has properties of a receptor for laminin and fibronectin. J Cell Biol. 1985 Dec;101(6):2134–2144. doi: 10.1083/jcb.101.6.2134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hosein B., Bianco C. Monocyte receptors for fibronectin characterized by a monoclonal antibody that interferes with receptor activity. J Exp Med. 1985 Jul 1;162(1):157–170. doi: 10.1084/jem.162.1.157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Kishimoto T. K., O'Connor K., Lee A., Roberts T. M., Springer T. A. Cloning of the beta subunit of the leukocyte adhesion proteins: homology to an extracellular matrix receptor defines a novel supergene family. Cell. 1987 Feb 27;48(4):681–690. doi: 10.1016/0092-8674(87)90246-7. [DOI] [PubMed] [Google Scholar]
  18. Kornblihtt A. R., Vibe-Pedersen K., Baralle F. E. Human fibronectin: cell specific alternative mRNA splicing generates polypeptide chains differing in the number of internal repeats. Nucleic Acids Res. 1984 Jul 25;12(14):5853–5868. doi: 10.1093/nar/12.14.5853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Markwell M. A., Fox C. F. Surface-specific iodination of membrane proteins of viruses and eucaryotic cells using 1,3,4,6-tetrachloro-3alpha,6alpha-diphenylglycoluril. Biochemistry. 1978 Oct 31;17(22):4807–4817. doi: 10.1021/bi00615a031. [DOI] [PubMed] [Google Scholar]
  20. Michl J., Pieczonka M. M., Unkeless J. C., Silverstein S. C. Effects of immobilized immune complexes on Fc- and complement-receptor function in resident and thioglycollate-elicited mouse peritoneal macrophages. J Exp Med. 1979 Sep 19;150(3):607–621. doi: 10.1084/jem.150.3.607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. O'Shea J. J., Brown E. J., Seligmann B. E., Metcalf J. A., Frank M. M., Gallin J. I. Evidence for distinct intracellular pools of receptors for C3b and C3bi in human neutrophils. J Immunol. 1985 Apr;134(4):2580–2587. [PubMed] [Google Scholar]
  23. Patel V. P., Lodish H. F. The fibronectin receptor on mammalian erythroid precursor cells: characterization and developmental regulation. J Cell Biol. 1986 Feb;102(2):449–456. doi: 10.1083/jcb.102.2.449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Plow E. F., Loftus J. C., Levin E. G., Fair D. S., Dixon D., Forsyth J., Ginsberg M. H. Immunologic relationship between platelet membrane glycoprotein GPIIb/IIIa and cell surface molecules expressed by a variety of cells. Proc Natl Acad Sci U S A. 1986 Aug;83(16):6002–6006. doi: 10.1073/pnas.83.16.6002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. Pommier C. G., O'Shea J., Chused T., Takahashi T., Ochoa M., Nutman T. B., Bianco C., Brown E. J. Differentiation stimuli induce receptors for plasma fibronectin on the human myelomonocytic cell line HL-60. Blood. 1984 Oct;64(4):858–866. [PubMed] [Google Scholar]
  27. Pommier C. G., O'Shea J., Chused T., Yancey K., Frank M. M., Takahashi T., Brown E. J. Studies on the fibronectin receptors of human peripheral blood leukocytes. Morphologic and functional characterization. J Exp Med. 1984 Jan 1;159(1):137–151. doi: 10.1084/jem.159.1.137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Pytela R., Pierschbacher M. D., Ginsberg M. H., Plow E. F., Ruoslahti E. Platelet membrane glycoprotein IIb/IIIa: member of a family of Arg-Gly-Asp--specific adhesion receptors. Science. 1986 Mar 28;231(4745):1559–1562. doi: 10.1126/science.2420006. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Ruggeri Z. M., Houghten R. A., Russell S. R., Zimmerman T. S. Inhibition of platelet function with synthetic peptides designed to be high-affinity antagonists of fibrinogen binding to platelets. Proc Natl Acad Sci U S A. 1986 Aug;83(15):5708–5712. doi: 10.1073/pnas.83.15.5708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. 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]
  32. Sanchez-Madrid F., Nagy J. A., Robbins E., Simon P., Springer T. A. A human leukocyte differentiation antigen family with distinct alpha-subunits and a common beta-subunit: the lymphocyte function-associated antigen (LFA-1), the C3bi complement receptor (OKM1/Mac-1), and the p150,95 molecule. J Exp Med. 1983 Dec 1;158(6):1785–1803. doi: 10.1084/jem.158.6.1785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Suzuki S., Argraves W. S., Pytela R., Arai H., Krusius T., Pierschbacher M. D., Ruoslahti E. cDNA and amino acid sequences of the cell adhesion protein receptor recognizing vitronectin reveal a transmembrane domain and homologies with other adhesion protein receptors. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8614–8618. doi: 10.1073/pnas.83.22.8614. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. 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]
  36. Wright S. D., Meyer B. C. Fibronectin receptor of human macrophages recognizes the sequence Arg-Gly-Asp-Ser. J Exp Med. 1985 Aug 1;162(2):762–767. doi: 10.1084/jem.162.2.762. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Wright S. D., Silverstein S. C. Tumor-promoting phorbol esters stimulate C3b and C3b' receptor-mediated phagocytosis in cultured human monocytes. J Exp Med. 1982 Oct 1;156(4):1149–1164. doi: 10.1084/jem.156.4.1149. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES