Tuftsin and Substance P as Modulators of Phagocyte Functions

  • Zvi Bar-Shavit
  • Rachel Goldman
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 141)


The basic tetrapeptide tuftsin, Thr-Lys-Pro-Arg, was described by Najjar and his collaborators as the entity responsible for the phagocytosis-enhancing activity of leukophilic γ-globulins. Since its discovery and synthesis, tuftsin was shown to affect many of the known functions of phagocytic cells. Tuftsin enhances phagocytosis, bactericidal activity, motility, cytotoxicity towards tumor target cells and immunogenic functions of macrophages. The tetra-peptide occupies the location 289–292 (Fc-region) in the amino acid sequence of all IgG subclasses and is released from the protein by a sequential two-step mechanism, involving a splenic carboxypeptidase and a surface leukokininase found on polymorphonuclear leukocytes (PMNL). The tetrapeptide exerts its activity only after its complete release from its parent molecule. (For reviews, see 1 and 2.)


Phagocytic Cell cGMP Level Mouse Peritoneal Macrophage Human Polymorphonuclear Leukocyte Carbamyl Choline 


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  1. 1.
    V. A. Najjar, Biological and biochemical characteristics of the tetrapeptide tuftsin, Thr-Lys-Pro-Arg, in:“Macrophages and Lymphocytes: Nature, Functions and Interaction”, Part A, R. Escobar and F. Friedman, eds., Plenum Press, New-York and London, pp.131–147 (1980).Google Scholar
  2. 2.
    M. Fridkin and P. Gottlieb, Tuftsin, Thr-Lys-Pro-Arg: Anatomy of an immunologically active peptide, Mol.Cell.Biochem., in press (1980).Google Scholar
  3. 3.
    Y. Stabinsky, P. Gottlieb, V. Zakuth, Z. Spirer and M. Fridkin, Specific binding sites for the phagocytosis stimulating peptide tuftsin on human polymorphonuclear leukocytes and monocytes, Biochem.Biophys.Res.Commun. 83: 599–606 (1978).PubMedCrossRefGoogle Scholar
  4. 4.
    Z. Bar-Shavit, Y. Stabinsky, M. Fridkin and R. Goldman, Tuftsinmacrophage interaction: Specific binding and augmentation of phagocytosis, J.Cell.Physiol. 100: 55–62 (1979).PubMedCrossRefGoogle Scholar
  5. 5.
    Z. Bar-Shavit, I. Bursuker and R. Goldman, Functional tuftsin binding sites on macrophage-like tumor line P388D1 and on bone marrow cells differentiated in vitro into mononuclear phagocytes, Mol.Cell.Biochem. 30: 151–155 (1980).PubMedCrossRefGoogle Scholar
  6. 6.
    J.D. Cox and M.D. Karnovsky, The depression of phagocytosis by exogenous cyclic nucleotides, prostaglandins, and theophylline, J.Cell.Biol. 59: 480–490 (1973).PubMedCrossRefGoogle Scholar
  7. 7.
    L. J. Ignarro and S.Y. Cech, Bidirectional regulation of lysosomal enzyme secretion and phagocytosis in human neutrophils by guanosine 3’,5 ’ -monophosphate and adenosine 3’,5’-monophosphate, Proc.Soc.Exp.Biol.Med. 151: 448–452 (1976).PubMedGoogle Scholar
  8. 8.
    Y. Stabinsky, Z. Bar-Shavit, M. Fridkin and R. Goldman, On the mechanism of action of the phagocytosis-stimulating peptide tufts in, Mol.Cell.Biochem. 30: 71–77 (1980).PubMedGoogle Scholar
  9. 9.
    A. Barthélemy, R. Paridaens and E. Schell-Frederick, Phagocytosis-induced 45calcium efflux in polymorphonuclear leukocytes, FEBS Letters 82: 283–287 (1977).PubMedCrossRefGoogle Scholar
  10. 10.
    S. T. Hoffstein, Ultrastructural demonstration of calcium loss from local regions of the plasma membrane of surface stimulated human granulocytes, J.Immunol. 123: 1395–1402 (1979).PubMedGoogle Scholar
  11. 11.
    M. J. Berridge and P. Rapp, Cyclic nucleotides, calcium and cellular control mechanisms, in: “Cyclic 3’,5’-Nucleotides: Mechanism of Action”, H. Cramer and J. Schultz, eds., J. Wiley & Sons, Chapter 5, pp. 65–76 (1977).Google Scholar
  12. 12.
    M. M. Chang, S.E. Leeman and H.D. Niall, Amino acid sequence of substance P, Nature New Biol. 232: 86–87 (1971).PubMedCrossRefGoogle Scholar
  13. 13.
    Z. Bar-Shavit, R. Goldman, Y. Stabinsky, P. Gottlieb, M. Fridkin, V.I. Teichberg and S. Blumberg, Enhancement of phagocytosis: A newly-found activity of substance P residing in its N-terminal tetrapeptide sequence, Biochem.Biophys. Res.Commun. 94: 1445–1451 (1980).PubMedCrossRefGoogle Scholar
  14. 14.
    T. Hokfelt, O. Johansson, J.-O. Kellerth, Â. Ljungdahl, G. Nilsson, A. Nygards and B. Pernow, Immunohistochemical distribution of substance P, in: “Substance P”, U.S. von Euler and B. Pernow, eds., Raven Press, New York, pp. 117–145 (1977).Google Scholar
  15. 15.
    R. A. Nicoll, C. Schenker and S. E. Leeman, Substance P as a transmitter candidate, in: “Ann.Rev.Neurosci.”, W.M. Cowan, Z.W. Hall and E.R. Handel, eds., Vol.3, pp. 227–268 (1980).Google Scholar
  16. 16.
    S. Rosell, U. Björkroth, D. Chang, I. Yamaguchi, Y.-P. Wan, G. Rackur, G. Fisher and K. Folkers, Effects of substance P and analogs on isolated guinea pig ileum, in: “Substance P”, U.S. von Euler and B. Pernow, eds., Raven Press, New-York, pp. 83–88 (1977).Google Scholar
  17. 17.
    R. W. Bury and M. L. Mashford, Biological activity of C-terminal partial sequences of substance P, J.Med.Chem. 19: 854–856 (1976).PubMedCrossRefGoogle Scholar
  18. 18.
    S. Blumberg and V. I. Teichberg, Biological activity and enzymic degradation of substance P analogs: Implications for studies of the substance P receptor, Biochem.Biophys.Res.Commun. 90: 347–354 (1979).PubMedCrossRefGoogle Scholar
  19. 19.
    S. Blumberg, V. I. Teichberg, J. L. Charli, L. B. Hersh and J. F. McKelvy, Cleavage of substance P to an N-terminal tetrapeptide and a C-terminal tetrapeptide by a post-proline cleaving enzyme from bovine brain, Fed.Proc. 38: 350 (1979).Google Scholar
  20. 20.
    J. W. Byron, Pharmacodynamic basis for the interaction of cimetidine with the bone marrow stem cells (CPUs), Exp.Hemat. 8: 256–263 (1980).PubMedGoogle Scholar
  21. 21.
    J. W. Byron, Mechanism for histamine H2-receptor-induced cell cycle changes in the bone marrow stem cell, Agents and Actions 7: 209–213 (1977).PubMedCrossRefGoogle Scholar
  22. 22.
    J. W. Byron, Evidence for a ß-adrenergic receptor initiating DNA synthesis in haemopoietic stem cells, Exp.Cell Res. 71: 228–232 (1972).PubMedCrossRefGoogle Scholar
  23. 23.
    J. W. Byron, Drug receptors and the haemopoietic stem cell, Nature (N.B.) 241: 152–154 (1973).Google Scholar
  24. 24.
    J. I. Kurland, J. W. Hadden and M. A. S. Moore, Role of cyclic nucleotides in the proliferation of committed granulocyte-macrophage progenitor cells, Canc.Res. 37: 4534–4538 (1977).Google Scholar
  25. 25.
    R. H. Schwartz, A. R. Bianco, C. R. Kahn and B. S. Handwerger, Demonstration that monocytes rather than lymphocytes are the insulin-binding cells in preparations of human peripheral blood mononuclear leukocytes: Implications for studies of insulin-resistant states in man, Proc.Natl.Acad.Sci.USA 72: 474–478 (1975).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1982

Authors and Affiliations

  • Zvi Bar-Shavit
    • 1
  • Rachel Goldman
    • 1
  1. 1.Department of Membrane ResearchThe Weizmann Institute of ScienceRehovotIsrael

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