Functional and Structural Interrelationships among the Mac-1, LFA-1 Family of Leukocyte Adhesion Glycoproteins, and their Deficiency in a Novel Heritable Disease

  • Timothy A. Springer
  • Donald C. Anderson


Cell surface adherence reactions are of central importance in the immune functions of lymphocytes, monocytes, and granulocytes. Lymphocytes adhere to antigen-presenting macrophages or dendritic cells in the induction of T-lym-phocyte immune responses, and to target cells in cell-mediated killing. Adhesive interactions are fundamental to a wide sprectrum of functions of granulocytes, monocytes, and macrophages. Specific recognition of opsonized microorganisms is facilitated by membrane receptors for IgG and for the third component of complement (C3), which mediate microbe-cell adhesion prior to the triggering of cytoskeletal events leading to endocytosis. Adhesion mediated by IgG (Fc) receptors can also trigger antibody-dependent killing of target cells, independently of endocytosis. In the absence of opsonins, some microorganisms/particles may adhere to granulocytes/monocytes without undergoing ingestion or may be phagocytized inefficiently, depending on the physical properties of the microorganisms.1


Chronic Granulomatous Disease Hairy Cell Leukemia Glycoprotein Family Autosomal Recessive Disease33 Structural Interrelationship 
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.


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  1. 1.
    Dawson, P., and Mandell, O., 1980, Phagocyte strategy vs. microbial tactics, Rev. Inf. Dis. 2:817–836.CrossRefGoogle Scholar
  2. 2.
    Carter, S. B., 1967, Haptotaxis and the mechanism of cell motility, Nature 213:256–260.PubMedCrossRefGoogle Scholar
  3. 3.
    Smith, C. W., Hollers, J. C., Patrick, R. A., and Hassett, C., 1979, Motility and adhesiveness in human neutrophils: Effects of chemotactic factors, J. Clin. Invest. 63:221–229.PubMedCrossRefGoogle Scholar
  4. 4.
    Atherton, A., and Born, G. V. R., 1972, Quantitative investigations of the adhesiveness of circulating polymorphonuclear leucocytes to blood vessel walls, J. Physiol. 222:447–474.PubMedGoogle Scholar
  5. 5.
    Keller, H. U., Barandum, S., Kistler, P., and Ploem, J., 1979, Locomotion and adhesion of neutrophil granulocytes: Effects of albumin, fibrinogen and gammaglobulins studied by reflexion contrast microscopy, Exp. Cell Res. 122:351–362.PubMedCrossRefGoogle Scholar
  6. 6.
    Wilkinson, P. C., and Lackie, J. M., 1979, The adhesion, migration and Chemotaxis of leukocytes in inflammation, Curr. Top. Path. 68:47–88.CrossRefGoogle Scholar
  7. 7.
    Köhler, G., and Milstein, C., 1975, Continuous cultures of fused cells secreting antibody of predefined specificity, Nature 256:495–497.PubMedCrossRefGoogle Scholar
  8. 8.
    Martz, E., 1977, Mechanism of specific tumor cell lysis by alloimmune T-lymphocytes: Resolution and characterization of discrete steps in the cellular interaction, Contemp. Top. Immunobiol. 7:301–361.CrossRefGoogle Scholar
  9. 9.
    Davignon, D., Martz, E., Reynolds, T., Kürzinger, K., and Springer, T. A., 1981, Lymphocyte function-associated antigen 1 (LFA-1): A surface antigen distinct from Lyt-2,3 that participates in T lymphocyte-mediated killing, Proc. Natl. Acad. Sci. USA 78:4535–4539.PubMedCrossRefGoogle Scholar
  10. 10.
    Sanchez-Madrid, F., Davignon, D., Martz, E., and Springer, T. A., 1982, Antigens involved in mouse cytolytic T-lymphocyte (CTL)-mediated killing: Functional screening and topographic relationship, Cell. Immunol. 73:1–11.PubMedCrossRefGoogle Scholar
  11. 11.
    Krensky, A. M., Sanchez-Madrid, F., Robbins, E., Nagy, J., Springer, T. A., and Burakoff, S. J., 1983, The functional significance, distribution, and structure of LFA-1, LFA-2, and LFA-3: Cell surface antigens associated with CTL-target interactions, J. Immunol. 131:611–616.PubMedGoogle Scholar
  12. 12.
    Springer, T. A., 1982, Quantitation of hybridoma immunoglobulins and selection of myeloma or specific light chain loss variants, Meth. Enzymol. 92:147–160.CrossRefGoogle Scholar
  13. 13.
    Davignon, D., Martz, E., Reynolds, T., Kürzinger, K., and Springer, T. A., 1981, Monoclonal antibody to a novel lymphocyte function-associated antigen (LFA-1): Mechanism of blocking of T lymphocyte-mediated killing and effects on other T and B lymphocyte functions, J. Immunol. 127:590–595.PubMedGoogle Scholar
  14. 14.
    Krensky, A. M., Robbins, E., Springer, T. A., and Burakoff, S. J., 1984, LFA-1, LFA-2 and LFA-3 antigens are involved in CTL-target conjugation, J. Immunol. 132:2180–2182.PubMedGoogle Scholar
  15. 15.
    Hildreth, J. E. K., Gotch, M. F., Hildreth, P. D. K., and McMichael, A. J., 1983, A human lymphocyte-associated antigen involved in cell-mediated lympholysis, Eur. J. Immunol. 13:202–208.PubMedCrossRefGoogle Scholar
  16. 16.
    Kohl, S., Springer, T. A., Schmalstieg, F. C., Loo, L. S., and Anderson, D. C., 1984, Defective natural killer cytotoxicity and polymorphonuclear leukocyte antibody-dependent cellular cytotoxicity in patients with LFA-l/OKM-1 deficiency, J. Immunol. 133:2972–2978.PubMedGoogle Scholar
  17. 17.
    Springer, T. A., Rothlein, R., Anderson, D. C., Burakoff, S. J., and Krensky, A. M., 1985, The function of LFA-1 in cell-mediated killing and adhesion: Studies on heritable LFA-1, Mac-1 deficiency and on lymphoid cell self-aggregation, in: Mechanisms of Cell-Mediated Cytotoxicity II, Plenum Press, New York, In press.Google Scholar
  18. 18.
    Kürzinger, K., Ho, M. K., and Springer, T. A., 1982, Structural homology of a macrophage differentiation antigen and an antigen involved in T-cell-mediated killing, Nature 296:668–670.PubMedCrossRefGoogle Scholar
  19. 19.
    Sanchez-Madrid, F., Nagy, J., Robbins, E., Simon, P., and Springer, T. A., 1983, A human leukocyte differentiation antigen family with distinct alpha subunits and a common beta sub-unit: The lymphocyte-function associated antigen (LFA-1), the C3bi complement receptor (OKM1-Mac-1), and the p 150,95 molecule, J. Exp. Med. 158:1785–1803.PubMedCrossRefGoogle Scholar
  20. 20.
    Unkeless, J. C., and Springer, T. A., 1984, Macrophages, in: Handbook of Experimental Immunology, 4th ed., Volume IV: Applications of Immunological Methods in Biomedical Sciences (D. M. Weir, C. C. Blackwell, L. A. Herzenberg, and L. A. Herzenberg, eds.), Blackwell, Oxford, In press.Google Scholar
  21. 21.
    Beller, D. I., Springer, T. A., and Schreiber, R. D., 1982, Anti-Mac-1 selectively inhibits the mouse and human type three complement receptor, J. Exp. Med. 156:1000–1009.PubMedCrossRefGoogle Scholar
  22. 22.
    Arnaout, M. A., Todd, R. F., III, Dana, N., Melamed, J., Schlossman, S. F., and Colten, H. R., 1983, Inhibition of phagocytosis of complement C3- or immunoglobulin G-coated particles and of C3bi binding by monoclonal antibodies to a monocyte-granulocyte membrane glycoprotein (Mol), J. Clin. Invest. 72:171–179.PubMedCrossRefGoogle Scholar
  23. 23.
    Wright, S. D., Rao, P. E., Van Voorhis, W. C., Craigmyle, L. S., Iida, K., Talle, M. A., Westberg, E. F., Goldstein, G., and Silverstein, S. C., 1983, Identification of the C3bi receptor of human monocytes and macrophages with monoclonal antibodies, Proc. Natl. Acad. Sci. USA 80:5699–5703.PubMedCrossRefGoogle Scholar
  24. 24.
    Sanchez-Madrid, F., Simon, P., Thompson, S., and Springer, T. A., 1983, Mapping of antigenic and functional epitopes on the alpha and beta subunits of two related glycoproteins involved in cell interactions, LFA-1 and Mac-1, J. Exp. Med. 158:586–602.PubMedCrossRefGoogle Scholar
  25. 25.
    Trowbridge, I. S., and Omary, M. B., 1981, Molecular complexity of leukocyte surface glycoproteins related to the macrophage differentiation antigen Mac-1, J. Exp. Med. 154:1517–1524.PubMedCrossRefGoogle Scholar
  26. 26.
    Kürzinger, K., and Springer, T. A., 1982, Purification and structural characterization of LFA-1, a lymphocyte function-associated antigen, and Mac-1, a related macrophage differentiation antigen, J. Biol. Chem. 257:12412–12418.PubMedGoogle Scholar
  27. 27.
    Ibrahimi, I. M., Prager, E. M., White, T. J., and Wilson, A. C., 1979, Amino acid sequence of California quail lysozyme. Effect of evolutionary substitutions on the antigenic structure of lysozyme, Biochemistry 13:2736–2744.CrossRefGoogle Scholar
  28. 28.
    Prager, E. M., Wilson, A. C., Perin, J. P., and Jolies, P., 1978, Further studies of an anomalous cross-reaction involving worm and vertebrate lysozymes, Immunochemistry 15:577–583.PubMedCrossRefGoogle Scholar
  29. 29.
    Springer, T. A., Sastre, L., Schmalstieg, F. C., and Anderson, D. C., 1985, Inherited LFA-1, Mac-1 deficiency and its molecular biology, in: Mononuclear Phagocytes and Inflammation (R. van Fürth and Z. A. Cohn, eds.), Martinus Nijhoff, in press.Google Scholar
  30. 30.
    Springer, T. A., Sastre, L., and Anderson, D. C., 1985, The LFA-1, Mac-1 Leukocyte adhesion glycoprotein family and its deficiency in a heritable human disease, Biochem. Soc. Trans. 13:3–6.PubMedGoogle Scholar
  31. 31.
    Springer, T. A., and Anderson, D. C., 1985, Antibodies specific for the Mac-1, LFA-1, pl50,95 glycoproteins or their family, or for other granulocyte proteins, in: Leukocyte Typing II (E. Reinherz, ed.), Springer-Verlag, Berlin, (in press).Google Scholar
  32. 32.
    Schwarting, R., Stein, H., and Wang, C. Y., 1984, The monoclonal antibodies anti S-HCL 1 (anti Leu 14) and anti S-HCL 3 (anti Leu M5) allow the diagnosis of hairy cell leukemia, Blood (in press).Google Scholar
  33. 33.
    Springer, T. A., Thompson, W. S., Miller, L. J., Schmalstieg, F. C., and Anderson, D. C., 1984, Inherited deficiency of the Mac-1, LFA-1, pi50,95 glycoprotein family and its molecular basis, J. Exp. Med. 160:1901–1918.PubMedCrossRefGoogle Scholar
  34. 34.
    Gallin, J. I., Fletcher, M. P., Seligman, B. E., Hoffstein, S., Cehes, K., and Mounessa, N., 1982, Human neutrophil-specific granule deficiency: A model to assess the role of neutrophil-specific granules in the evolution of the inflammatory response, Blood 59:1317–1329.PubMedGoogle Scholar
  35. 35.
    Crowley, C. A., Curnutte, J. T., Rosin, R. E., Andre-Schwartz, J., Gallin, J. I., Klempner, M., Snyderman, R., Southwick, F. S., Stossel, T. P., and Babior, B. M., 1980, An inherited abnormality of neutrophil adhesion: Its genetic transmission and its association with a missing protein, N. Engl. J. Med. 302:1163–1168.PubMedCrossRefGoogle Scholar
  36. 36.
    Buchanan, M. R., Crowley, C. A., Rosin, R. E., Gimbrone, M.A., and Babior, B. M., 1982, Studies on the interaction between GP-180-deficient neutrophils and vascular endothelium, Blood 60:160–165.PubMedGoogle Scholar
  37. 37.
    Arnaout, M. A., Pitt, J., Cohen, H. J., Melamed, J., Rosen, F. S., and Colten, H. R., 1982, Deficiency of a granulocyte-membrane glycoprotein (gpl50) in a boy with recurrent bacterial infections, N. Engl. J. Med. 306:693–699.PubMedCrossRefGoogle Scholar
  38. 38.
    Anderson, D. C., Schmalstieg, F. C., Kohl, S., Arnaout, M. A., Hughes, B. J., Tosi, M. F., Buffone, G. J., Brinkley, B. R., Dickey, W. D., Abramson, J. S., Springer, T. A., Boxer, L. A., Hollers, J. M., and Smith, C. W., 1984, Abnormalities of polymorphonuclear leukocyte function associated with a heritable deficiency of high molecular weight surface glycoproteins (GP138): Common relationship to diminished cell adherence, J. Clin. Invest. 74:536–551.PubMedCrossRefGoogle Scholar
  39. 39.
    Anderson, D. C., Schmalstieg, F. C., Finegold, M. J., Hughes, B. J., Rothlein, R., Miller, L. J., Kohl, S., Tosi, M. F., Jacobs, R. L., Waldrop, T. C., Goldman, A., Shearer, W. T., and Springer, T. A., 1985, The severe and moderate phenotypes of heritable Mac-1, LFA-1 deficiency: their quantitative definition and relation to leukocyte dysfunction and clinical features, J. Inf. Dis. (in press).Google Scholar
  40. 40.
    Springer, T. A., 1985, The LFA-1, Mac-1 glycoprotein family and its deficiency in an inherited disease: Introduction, Fed.Proc. (in press).Google Scholar
  41. 41.
    Dana, N., Todd, R. F., III, Pitt, J., Springer, T. A. and Arnaout, M. A., 1984, Deficiency of a surface membrane glycoprotein (Mol) in man, J. Clin. Invest. 73:153–159.PubMedCrossRefGoogle Scholar
  42. 42.
    Anderson, D. C., Schmalstieg, F. C., Shearer, W., Freeman, K., Kohl, S., Smith, C. W., and Springer, T., 1985, Abnormalities of PMN monocyte function and recurrent infection associated with a heritable deficiency of adhesive surface glycoproteins, Fed. Proc. (in press).Google Scholar
  43. 43.
    Fearon, D. T., and Collins, L. A., 1983, Increased expression of C3b receptors on polymorphonuclear leukocytes induced by chemotactic factors and by purification procedures, J. Immunol. 130:370–375.PubMedGoogle Scholar
  44. 44.
    Ho, M. K., and Springer, T. A., 1982, Mac-1 antigen: Quantitative expression in macrophage populations and tissues, and immunofluorescent localization in spleen, J. Immunol. 128:2281–2286.PubMedGoogle Scholar
  45. 45.
    Arnaout, M. A., Dana, N., Pitt, J., and Todd, R. F., Ill, 1985, Deficiency of two human leukocyte surface membrane glycoproteins (Mol and LFA-1), Fed. Proc. (in press).Google Scholar
  46. 46.
    Beatty, P. C., Harlan, J. M., Rosen, H., Hansen, J. A., Ochs, H. D., Price, T. D., Taylor, R. F., and Klebanoff, S. J., 1984, Absence of monoclonal-antibody-defined protein complex in boy with abnormal leucocyte function, Lancet 1:535–537.PubMedCrossRefGoogle Scholar
  47. 47.
    Ross, G. D., Thompson, R. A., Walport, M. J., Springer, T. A., Watson, J. V., Ward, R. H. R., Lida, J., Newman, S. L., Harrison, R. A., and Lachmann, P. J., 1984, Characterization of patients with an increased susceptibility to bacterial infections and a genetic deficiency of leukocyte membrane complement receptor type three (CR3) and the related membrane antigen LFA-1, Blood, manuscript submitted.Google Scholar
  48. 48.
    Fischer, A., Seger, R., Durandy, A., Grospierre, B., Virelizier, J. L., Griscelli, C., Fischer, E., Kazatchkine, M., Bohler, M. C., Descamps-Latscha, B., Trung, P. H., Springer, T. A., Olive, D., and Mawas, C., 1984, Deficiency of the adhesive protein complex LFA-1, C3bi complement receptor, pl50,95 in a girl with recurrent bacterial infections, Blood (in press).Google Scholar
  49. 49.
    Sanchez-Madrid, F., Krensky, A. M., Ware, C. F., Robbins, E., Strominger, J. L., Burakoff, S. J., and Springer, T. A., 1982, Three distinct antigens associated with human T lymphocyte-mediated cytolysis: LFA-1, LFA-2, and LFA-3, Proc. Natl. Acad. Sci. USA 79:7489–7493.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Timothy A. Springer
    • 1
    • 2
  • Donald C. Anderson
    • 3
  1. 1.Laboratory of Membrane ImmunochemistryDana-Farber Cancer InstituteBostonUSA
  2. 2.Department of PathologyHarvard Medical SchoolBostonUSA
  3. 3.Department of PediatricsBaylor College of MedicineHoustonUSA

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