Skip to main content
PMC home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1976 Sep 1;70(3):719–723. doi: 10.1083/jcb.70.3.719

Cytotoxicity for tumor cells of cationic proteins from human neutrophil granules

PMCID: PMC2109852  PMID: 182702

Abstract

Cationic proteins purified from human polymorphonuclear leukocyte granules exert a cytotoxic effect on mammalian tumor cells. This effect is time and concentration dependent, is inhibited by the anionic agent heparin, and is enhanced by preheating the cationic proteins. Other strongly basic proteins (histone, protamine) also exhibited cytotoxic activity. Myeloperoxidase isolated from human leukocytes is cytotoxic when combined with H2O2 and chloride. Under these conditions, the potency of the myeloperoxidase-mediated system is greater than that of the cationic proteins.

Full Text

The Full Text of this article is available as a PDF (369.0 KB).

Selected References

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

  1. Baehner R. L., Karnovsky M. J., Karnovsky M. L. Degranulation of leukocytes in chronic granulomatous disease. J Clin Invest. 1969 Jan;48(1):187–192. doi: 10.1172/JCI105967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bainton D. F. Sequential degranulation of the two types of polymorphonuclear leukocyte granules during phagocytosis of microorganisms. J Cell Biol. 1973 Aug;58(2):249–264. doi: 10.1083/jcb.58.2.249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Becker E. L., Showell H. J., Henson P. M., Hsu L. S. The ability of chemotactic factors to induce lysosomal enzyme release. I. The characteristics of the release, the importance of surfaces and the relation of enzyme release to chemotactic responsiveness. J Immunol. 1974 Jun;112(6):2047–2054. [PubMed] [Google Scholar]
  4. Clark R. A., Klebanoff S. J., Einstein A. B., Fefer A. Peroxidase-H2O2-halide system: Cytotoxic effect on mammalian tumor cells. Blood. 1975 Feb;45(2):161–170. [PubMed] [Google Scholar]
  5. Clark R. A., Klebanoff S. J. Neutrophil-mediated tumor cell cytotoxicity: role of the peroxidase system. J Exp Med. 1975 Jun 1;141(6):1442–1447. doi: 10.1084/jem.141.6.1442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Edelson P. J., Cohn Z. A. Peroxidase-mediated mammalian cell cytotoxicity. J Exp Med. 1973 Jul 1;138(1):318–323. doi: 10.1084/jem.138.1.318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gale R. P., Zighelboim J. Modulation of polymorphonuclear leukocyte-mediated antibody-dependent cellular cytotoxicity. J Immunol. 1974 Dec;113(6):1793–1800. [PubMed] [Google Scholar]
  8. Gale R. P., Zighelboim J. Polymorphonuclear leukocytes in antibody-dependent cellular cytotoxicity. J Immunol. 1975 Mar;114(3):1047–1051. [PubMed] [Google Scholar]
  9. Goldstein I., Hoffstein S., Gallin J., Weissmann G. Mechanisms of lysosomal enzyme release from human leukocytes: microtubule assembly and membrane fusion induced by a component of complement. Proc Natl Acad Sci U S A. 1973 Oct;70(10):2916–2920. doi: 10.1073/pnas.70.10.2916. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hawkins D. Neutrophilic leukocytes in immunologic reactions in vitro: effect of cytochalasin B. J Immunol. 1973 Jan;110(1):294–296. [PubMed] [Google Scholar]
  11. Hawkins D. Neutrophilic leukocytes in immunologic reactions: evidence for the selective release of lysosomal constituents. J Immunol. 1972 Feb;108(2):310–317. [PubMed] [Google Scholar]
  12. Henson P. M. Interaction of cells with immune complexes: adherence, release of constituents, and tissue injury. J Exp Med. 1971 Sep 1;134(3 Pt 2):114s–135s. [PubMed] [Google Scholar]
  13. Henson P. M., Johnson H. B., Spiegelberg H. L. The release of granule enzymes from human neutrophils stimulated by aggregated immunoglobulins of different classes and subclasses. J Immunol. 1972 Dec;109(6):1182–1192. [PubMed] [Google Scholar]
  14. Henson P. M., Oades Z. G. Enhancement of immunologically induced granule exocytosis from neutrophils by cytochalasin B. J Immunol. 1973 Jan;110(1):290–293. [PubMed] [Google Scholar]
  15. Henson P. M. The immunologic release of constituents from neutrophil leukocytes. I. The role of antibody and complement on nonphagocytosable surfaces or phagocytosable particles. J Immunol. 1971 Dec;107(6):1535–1546. [PubMed] [Google Scholar]
  16. Ignarro L. J., George W. J. Mediation of immunologic discharge of lysosomal enzymes from human neutrophils by guanosine 3',5'-monophosphate. Requirement of calcium, and inhibition by adenosine 3',5'-monophosphate. J Exp Med. 1974 Jul 1;140(1):225–238. doi: 10.1084/jem.140.1.225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Klebanoff S. J. Antimicrobial mechanisms in neutrophilic polymorphonuclear leukocytes. Semin Hematol. 1975 Apr;12(2):117–142. [PubMed] [Google Scholar]
  18. Klebanoff S. J., Clark R. A. Hemolysis and iodination of erythrocyte components by a myeloperoxidase-mediated system. Blood. 1975 May;45(5):699–707. [PubMed] [Google Scholar]
  19. Klebanoff S. J. Iodination of bacteria: a bactericidal mechanism. J Exp Med. 1967 Dec 1;126(6):1063–1078. doi: 10.1084/jem.126.6.1063. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Klebanoff S. J. Myeloperoxidase-halide-hydrogen peroxide antibacterial system. J Bacteriol. 1968 Jun;95(6):2131–2138. doi: 10.1128/jb.95.6.2131-2138.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lehrer R. I. Antifungal effects of peroxidase systems. J Bacteriol. 1969 Aug;99(2):361–365. doi: 10.1128/jb.99.2.361-365.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lehrer R. I., Ladra K. M., Hake R. B. Nonoxidative fungicidal mechanisms of mammalian granulocytes: demonstration of components with candidacidal activity in human, rabbit, and guinea pig leukocytes. Infect Immun. 1975 Jun;11(6):1226–1234. doi: 10.1128/iai.11.6.1226-1234.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. McRipley R. J., Sbarra A. J. Role of the phagocyte in host-parasite interactions. XII. Hydrogen peroxide-myeloperoxidase bactericidal system in the phagocyte. J Bacteriol. 1967 Nov;94(5):1425–1430. doi: 10.1128/jb.94.5.1425-1430.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Odeberg H., Olsson I. Antibacterial activity of cationic proteins from human granulocytes. J Clin Invest. 1975 Nov;56(5):1118–1124. doi: 10.1172/JCI108186. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Odeberg H., Olsson I., Venge P. Cationic proteins of human granulocytes. IV. Esterase activity. Lab Invest. 1975 Jan;32(1):86–90. [PubMed] [Google Scholar]
  26. Olsson I., Olofsson T., Odeberg H. Myeloperoxidase-mediated iodination in granulocytes. Scand J Haematol. 1972;9(5):483–491. doi: 10.1111/j.1600-0609.1972.tb00974.x. [DOI] [PubMed] [Google Scholar]
  27. Olsson I., Venge P. Cationic proteins of human granulocytes. II. Separation of the cationic proteins of the granules of leukemic myeloid cells. Blood. 1974 Aug;44(2):235–246. [PubMed] [Google Scholar]
  28. Ranadive N. S., Sajnani A. N., Alimurka K., Movat H. Z. Release of basic proteins and lysosomal enzymes from neutrophil leukocytes of the rabbit. Int Arch Allergy Appl Immunol. 1973;45(6):880–898. doi: 10.1159/000231087. [DOI] [PubMed] [Google Scholar]
  29. Rindler-Ludwig R., Braunsteiner H. Cationic proteins from human neutrophil granulocytes. Evidence for their chymotrypsin-like properties. Biochim Biophys Acta. 1975 Feb 27;379(2):606–617. doi: 10.1016/0005-2795(75)90167-1. [DOI] [PubMed] [Google Scholar]
  30. Smith D. C., Klebanoff S. J. A uterine fluid-mediated sperm-inhibitory system. Biol Reprod. 1970 Oct;3(2):229–235. doi: 10.1093/biolreprod/3.2.229. [DOI] [PubMed] [Google Scholar]
  31. Weissmann G., Zurier R. B., Spieler P. J., Goldstein I. M. Mechanisms of lysosomal enzyme release from leukocytes exposed to immune complexes and other particles. J Exp Med. 1971 Sep 1;134(3 Pt 2):149s–165s. [PubMed] [Google Scholar]
  32. Zeya H. I., Spitznagel J. K. Arginine-rich proteins of polymorphonuclear leukocyte lysosomes. Antimicrobial specificity and biochemical heterogeneity. J Exp Med. 1968 May 1;127(5):927–941. doi: 10.1084/jem.127.5.927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Zeya H. I., Spitznagel J. K. Cationic proteins of polymorphonuclear leukocyte lysosomes. II. Composition, properties, and mechanism of antibacterial action. J Bacteriol. 1966 Feb;91(2):755–762. doi: 10.1128/jb.91.2.755-762.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Zurier R. B., Hoffstein S., Weissmann G. Cytochalasin B: effect on lysosomal enzyme release from human leukocytes. Proc Natl Acad Sci U S A. 1973 Mar;70(3):844–848. doi: 10.1073/pnas.70.3.844. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES