Specificity and Regulation of CD18-Dependent Adhesions

  • Samuel D. Wright
  • Siu Kong Lo
  • Patricia A. Detmers


The ability of polymorphonuclear leukocytes (PMN) to adhere to other cells and substrates is under strict physiological regulation. This is best illustrated by considering PMN circulating within the vasculature. These cells show negligible affinity for the endothelial cells (EC) which surround them. When PMN encounter chemotactic factors this situation is rapidly altered, and the adhesion of PMN to EC is dramatically enhanced. In normal circumstances, stimulated PMN soon break their adhesion to EC and either return to the circulation or leave the vasculature by diapedesis. Thus, PMN possess the means of transiently making then breaking adhesion to EC and other substrates in response to specific stimuli.


Phorbol Myristate Acetate Phorbol Myristate Acetate Vitronectin Receptor Fibronectin Receptor Neural Crest Cell Migration 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Wright SD, Rao PE, Van Voorhis WC, Craigmyle LS, Iida K, Talle MA, Westberg EF, Goldstein G, Silverstein SC: Identification of the C3bi receptor on human monocytes and macrophages by using monoclonal antibodies. Proc Natl Acad Sci USA 80:5699–5703, 1983.PubMedCrossRefGoogle Scholar
  2. 2.
    Wright SD, Weitz JI, Huang AJ, Levin SM, Silverstein SC, Loike JD: Complement receptor type three (CR3, CD11b/CD18) of human polymorphonuclear leukocytes recognizes fibrinogen. Proc Natl Acad Sci USA 85:7734–7738, 1988.PubMedCrossRefGoogle Scholar
  3. 3.
    Dana N, Styrt B, Griffin JD, Todd III RF, Klempner MS, Arnaout MA: Two functional domains in the phagocyte membrane glycoprotein Mol identified with monoclonal antibodies. J Immunol 137:3259–3263, 1986.PubMedGoogle Scholar
  4. 4.
    Harlan JM, Killen PD, Senecal FM, Schwartz BR, Yee EK, Taylor FR, Beatty PG, Price TH, Ochs HH: The role of neutrophil membrane protein GP-150 in neutrophil adhesion to endothelia in vitro. Blood 66:167–178, 1985.PubMedGoogle Scholar
  5. 5.
    Lo SK, Detmers PA, Levin SM, Wright SD: Transient adhesion of neutrophils to endothelium. J Exp Med 169:1779–1793, 1989.PubMedCrossRefGoogle Scholar
  6. 6.
    Arfors K-E, Lunderg C, Lindblom L, Lundberg K, Beatty PG, Harlan JM: A monoclonal antibody to the membrane glycoprotein complex CD18 inhibits polymorphonuclear leukocyte accumulation and plasma leakage in vivo. Blood 69:338–340, 1987.PubMedGoogle Scholar
  7. 7.
    Rosen H, Gordon S: Monoclonal antibody to the murine type 3 complement receptor inhibits adhesion of myelomonocytic cells in vitro and inflammatory cell recruitment in vivo. J Exp Med 166:1685–1701, 1987.PubMedCrossRefGoogle Scholar
  8. 8.
    Tuomanen EI, Saukkonen K, Sande S, Cioffe C, Wright SD: Reduction of inflammation, tissue damage, and mortality in bacterial meningitis in rabbits treated with monoclonal antibodies against adhesion-promoting receptors of leukocytes. J Exp Med (in press), 1989.Google Scholar
  9. 9.
    Todd III RF, Freyer DR: The CD11/CD18 leukocyte glycoprotein deficiency. Hem/Onc Clin N Am 2:13–31, 1988.Google Scholar
  10. 10.
    Wright SD, Detmers PA: Adhesion-promoting receptors on phagocytes. J Cell Sci Suppl 9:99–120, 1988.PubMedGoogle Scholar
  11. 11.
    Wright SD, Reddy PA, Jong MTC, Erickson BW: C3bi receptor (complement receptor type 3) recognizes a region of complement protein C3 containing the sequence Arg-Gly-Asp. Proc Natl Acad Sci USA 84:1965–1968, 1987.PubMedCrossRefGoogle Scholar
  12. 12.
    Ruoslahti E, and Pierschbacher MD: Arg-Gly-Asp: A versatile cell recognition signal. Cell 44:517–518, 1986.PubMedCrossRefGoogle Scholar
  13. 13.
    Hynes RO: Integrins: A family of cell surface receptors. Cell 48:549–554, 1987.PubMedCrossRefGoogle Scholar
  14. 14.
    Law SKA, Gagnon J, Hildreth JE, Wells CE, Willis AC, Wong AJ: The primary structure of the beta-subunit of the cell surface adhesion glycoproteins LFA-1, CR3 and p150,95 and its relationship to the fibronectin receptor. EMBO 7 6:915,1987.Google Scholar
  15. 15.
    Kishimoto TK, O’Connor K, Lee A, Roberts TM, Springer TA: Cloning of the beta subunit of the leukocyte adhesion proteins: Homology to an extra-cellular matrix receptor defines a novel supergene family. Cell 48:681–690, 1987.PubMedCrossRefGoogle Scholar
  16. 16.
    Corbi AL, Miller LJ, O’Conner K, Larson RS, Springer TA: cDNA cloning and complete primary structure of the alpha subunit of a leukocyte adhesion glycoprotein, pl50,95. EMBO J 6:4023–4028, 1987.PubMedGoogle Scholar
  17. 17.
    Arnaout MA, Gupta SK, Pierce MW, Tenen DG: Amino acid sequence of the alpha subunit of human leukocyte adhesion receptor Mo1 (Complement receptor type 3). J Cell Biol 106:2153–2158, 1988.PubMedCrossRefGoogle Scholar
  18. 18.
    Wright SD, Silverstein SC: Receptors for C3b and C3bi promote phagocytosis but not the release of toxic oxygen from human phagocytes. J Exp Med 158:2016–2023, 1983.PubMedCrossRefGoogle Scholar
  19. 19.
    Aderem AA, Wright SD, Silverstein SC, Cohn ZA: Ligated complement receptors do not activate the arachidonic acid cascade in resident peritoneal macrophages. J Exp Med 161:617–622, 1985.PubMedCrossRefGoogle Scholar
  20. 20.
    Button LL, McMaster WR: Molecular cloning of the major surface antigen of Leishmania. J Exp Med 167:724, 1988.PubMedCrossRefGoogle Scholar
  21. 21.
    Russell DG, Wright SD: Complement receptor type 3 (CR3) binds to an Arg-Gly-Asp-containing region of the major surface glycoprotein, gp63, of Leishmania promastigotes. J Exp Med 168: 279–292, 1988.PubMedCrossRefGoogle Scholar
  22. 22.
    Wright SD, Silverstein SC: Phagocytosing macrophages exclude proteins from the zones of contact with opsonized targets. Nature 309:359–361, 1984.PubMedCrossRefGoogle Scholar
  23. 23.
    Weitz JI, Huang AJ, Landman SL, Nicholson SC, Silverstein SC: Elastase-mediated fibrinogenolysis by chemoattractant-stimulated neutrophils occurs in the presence of physiological concentrations of antiproteinases. J Exp Med 166:1836–1850, 1987.PubMedCrossRefGoogle Scholar
  24. 24.
    Lam SCT, Plow EF, Smith MA, Andrieux A, Ryckwaert JJ, Marguerie G, Ginsberg MH: Evidence that arginyl-glycyl-aspartate peptides and fibrinogen gamma chain peptides share a common binding site on platelets. J Biol Chem 262:947–950, 1987.PubMedGoogle Scholar
  25. 25.
    Wright SD, Meyer BC: The fibronectin receptor of human macrophages recognizes the amino acid sequence, Arg-Gly-Asp-Ser. J Exp Med 162:762–766, 1985.PubMedCrossRefGoogle Scholar
  26. 26.
    Ezekowitz, RAB, Sim RB, Hill M, Gordon S: Local opsonization by secreted macrophage complement components. Role of receptors for complement in uptake of zymosan. J Exp Med 159:244–260, 1984.PubMedCrossRefGoogle Scholar
  27. 27.
    Ross GD, Cain JA, Lachmann PJ: Membrane complement receptor type three (CR3) has lectin-like properties analogous to bovine conglutinin and functions as a receptor for zymosan and rabbit erythrocytes as well as a receptor for iC3b. J Immunol 134:3307–3315, 1985.PubMedGoogle Scholar
  28. 28.
    Ross GD, Thompson RA, Walport MJ, Springer TA, Watson JV, Ward RHR, Lida J, Newman SL, Harrison RA, Lachmann PJ: Characterization of patients with an increased susceptibility to bacterial infections and a genetic deficiency of leukocyte membrane complement receptor type 3 and the related membrane antigen LFA-1. Blood 66:882–890, 1985.PubMedGoogle Scholar
  29. 29.
    Wright SD, Levin SM, Jong MTC, Chad Z, Kabbash LG: CR3 (CD11b/CD18) expresses one binding site for Arg-Gly-Asp-containing peptides, and a second site for bacterial lipopolysaccharide. J Exp Med 169:175–183, 1989.PubMedCrossRefGoogle Scholar
  30. 30.
    Bullock WE, Wright SD: The role of adherence-promoting receptors, CR3, LFA-1, and p150,95 in binding of Histoplasma capsulatum by human macrophages. J Exp Med 165:195–210, 1987.PubMedCrossRefGoogle Scholar
  31. 31.
    Wright SD, Jong MTC: Adhesion-promoting receptors on human macrophages recognize E. coli by binding to lipopolysaccharide. J Exp Med 164:1867–1888, 1986.Google Scholar
  32. 32.
    Morrison DC, Ulevitch JR: The effects of bacterial endotoxins on host mediating systems. Am J Pathol 93:527–617, 1978.Google Scholar
  33. 33.
    Beutler B, Mahoney J, LeTrang N, Pekala P, Cerami A: Purification of cach-ectin, a lipoprotein lipase-supressing hormone secreted by endotoxin-treated RAW 264.7 cells. J Exp Med 161:984–995, 1985.PubMedCrossRefGoogle Scholar
  34. 34.
    Durum SK, Schmidt JA, Oppenheim JJ: Interleukin-1: An immunological perspective. Ann Rev Immunol 3:263–287, 1985.CrossRefGoogle Scholar
  35. 35.
    Suzuki S, Oldberg A, Hayman EG, Pierschbacher MD, Ruoslahti E: Complete amino acid sequence of human vitronectin deduced from cDNA. Similarity of cell attachment sites in vitronectin and fibronectin. EMBO 74:2519–2524, 1985.Google Scholar
  36. 36.
    Cheresh, DA, Pytela R, Pierschbacher MD, Klier FG, Ruoslahti E, Reisfeld RA: An Arg-Gly-Asp-directed receptor on the surface of human melanoma cells exists in a divalent cation-dependent functional complex with disialo-ganglioside GD2. J Cell Biol 105:1163–1173, 1987.PubMedCrossRefGoogle Scholar
  37. 37.
    Lo SK, Wright SD: CR3 mediates binding of PMN to endothelial cells (EC) via its RGD binding, not the LPS binding site. FASEB J 2:A991, 1988.Google Scholar
  38. 38.
    Marlin SD, Springer TA. 1987. Purified intercellular adhesion molecule-1 (ICAM-1) is a ligand for lymphocyte function-associated antigen (LFA-1). Cell 51:813–819, 1987.Google Scholar
  39. 39.
    Rovasio, RA, Delouvee A, Yamada KM, Timpl R, Thiery JP. Neural crest cell migration: Requirements for exogenous fibronectin and high cell density. J Cell Biol 96:462–473, 1983.PubMedCrossRefGoogle Scholar
  40. 40.
    Sanderson CJ: 1976. The mechanism of T cell mediated cytotoxicity. II. Morphological studies of cell death by time-lapse microcinematography. Proc R Soc Lond Ser B 92:241–255, 1976.Google Scholar
  41. 41.
    Boucaut JC, Darribere T, Poole TJ, Aoyama H, Yamada KM, Thiery JP: Biologically active synthetic peptides as probes of embryonic development: A competitive peptide inhibitor of fibronectin function inhibits gastrulation in amphibian embryos and neural crest cell migration in avian embryos. J Cell Biol 99:1822–1830, 1984.PubMedCrossRefGoogle Scholar
  42. 42.
    Naidet C, Semeriva M, Yamada KM, Thiery JP: Peptides containing the cell-attachment recognition signal Arg-Gly-Asp prevent gastrulation in Drosophila embryos. Nature 325:348–350, 1987.PubMedCrossRefGoogle Scholar
  43. 43.
    Hirst R, Horwitz A, Buck C, Rohrschneider L: Phosphorylation of the fibronectin receptor complex in cells transformed by oncogenes that encode tyrosine kinases. Proc Natl Acad Sci USA 83:6470–6474, 1986.PubMedCrossRefGoogle Scholar
  44. 44.
    Chen W-T, Wang J, Hasegawa T, Yamada SS, Yamada KM: Regulation of fibronectin receptor distribution by transformation, exogenous fibronectin, and synthetic peptides. J Cell Biol 103:1649–1661, 1986.PubMedCrossRefGoogle Scholar
  45. 45.
    Rothlein R, Springer TA: The requirement for lymphocyte function-associated antigen 1 in homotypic leukocyte adhesion stimluated by phorbol esters. J Exp Med 163:1132–1149, 1986.PubMedCrossRefGoogle Scholar
  46. 46.
    Wright SD, Silverstein SC: Tumor-producing phorbol esters stimulate C3b and C3b’ receptor-mediated phagocytosis in cultured human monocytes. J Exp Med 156:1149–1164, 1982.PubMedCrossRefGoogle Scholar
  47. 47.
    Wright SD, Detmers PA, Jong MTC, Meyer BC: Interferon-gamma depresses binding of ligand by C3b and C3bi receptors on cultured human monocytes, an effect reversed by fibronectin. J Exp Med 163:1245–1259, 1986.PubMedCrossRefGoogle Scholar
  48. 48.
    Guyre PM, Morganelli PM, Miller R: Recombinant immune interferon increases immunoglobulin G Fc receptors on cultured human mononuclear phagocytes. J Clin Invest 72:393–397, 1983.PubMedCrossRefGoogle Scholar
  49. 49.
    Wright SD, Meyer BC: Phorbol esters cause sequential activation and deactivation of complement receptors on polymorphonuclear leukocytes. J Immunol 136:1759–1764, 1986.PubMedGoogle Scholar
  50. 50.
    Berger M, O’Shea J, Cross AS, Folks TM, Chused TM, Brown EJ, Frank MM. Human neutrophils increase expression of C3bi as well as C3b receptors upon activation. J Clin Invest 74:1566, 1984.PubMedCrossRefGoogle Scholar
  51. 51.
    O’Shea J, Brown EJ, Seligmann BE, Metcalf JA, Frank MM, Gallin JI: Evidence for distinct intracellular pools of receptors for C3b and C3bi in human neutrophils. J Immunol 134:2580, 1985.PubMedGoogle Scholar
  52. 52.
    Todd III RF, Arnaout MA, Rosin RE, Crowley CA, Peters WA, Babior BM: Subcellular localization of the large subunit of Mol (Mol: formerly gp 110), a surface glycoprotein associated with neutrophil adhesion. J Clin Invest 74:1280, 1984.PubMedCrossRefGoogle Scholar
  53. 53.
    Petrequin PR, Todd III RF, Devall LJ, Boxer LA, Curnutte III JT: Association between gelatinase release and increased plasma membrane expression of the Mol glycoprotein. Blood 69:605–610, 1987.PubMedGoogle Scholar
  54. 54.
    Borregaard N, Miller LJ, Springer TA: Chemoattractant-regulated mobilization of anovel intracellular compartment in human neutrophils. Science 237:1204–1206, 1987.PubMedCrossRefGoogle Scholar
  55. 55.
    Detmers PA, Wright SD, Olsen E, Kimball B, Cohn ZA: Aggregation of complement receptors on human neutrophils in the absence of ligand. J Cell Biol 105:1137–1145, 1987.PubMedCrossRefGoogle Scholar
  56. 56.
    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 257:7847–7851, 1982.PubMedGoogle Scholar
  57. 57.
    Hermanowski-Vosatka A, Detmers PA, Goetze O, Silverstein SC, Wright SD: Clustering of binding sites on the plasma membrane enhances cell-cell adhesion. J Biol Chem 263:17,822–17,827, 1988.Google Scholar

Copyright information

© Springer-Verlag New York Inc. 1990

Authors and Affiliations

  • Samuel D. Wright
  • Siu Kong Lo
  • Patricia A. Detmers

There are no affiliations available

Personalised recommendations