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. 1989 Jan 1;169(1):99–113. doi: 10.1084/jem.169.1.99

Antibacterial activity of human natural killer cells

PMCID: PMC2189196  PMID: 2642532

Abstract

The in vitro effects of human NK cells on viability of Gram-negative and Gram-positive bacteria was investigated. PBLs depleted of glass- adherent cells showed a significant antibacterial activity that was increased as the concentration of NK cells became higher. Leu-11- enriched cells exhibited the most efficient bactericidal activity. Stimulation of NK cells with staphylococcal enterotoxin B for 16 h produced a significant increase in the antibacterial activity of all NK cells tested. The antibacterial activity of monocyte-depleted cells and Leu-11-enriched cells was also enhanced after culturing in vitro for 16- 24 h without exogenous cytokines. Dependence of the antibacterial activity on the presence of serum in the culture medium was not found. Ultrastructural studies revealed close contact between NK cell membranes and bacteria, no evidence of phagocytosis, and extracellular bacterial ghosts, after incubation at 37 degrees C. Supernatants from purified NK cells exhibited potent bactericidal activity with kinetics and target specificity similar to that of effector cells. These results document the potent antibacterial activity of purified NK cells and suggest an extracellular mechanism of killing.

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Selected References

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  1. Abo T., Sugawara S., Amenomori A., Itoh H., Rikiishi H., Moro I., Kumagai K. Selective phagocytosis of gram-positive bacteria and interleukin 1-like factor production by a subpopulation of large granular lymphocytes. J Immunol. 1986 May 1;136(9):3189–3197. [PubMed] [Google Scholar]
  2. Bonavida B., Wright S. C. Role of natural killer cytotoxic factors in the mechanism of target-cell killing by natural killer cells. J Clin Immunol. 1986 Jan;6(1):1–8. doi: 10.1007/BF00915358. [DOI] [PubMed] [Google Scholar]
  3. Bukowski J. F., Woda B. A., Habu S., Okumura K., Welsh R. M. Natural killer cell depletion enhances virus synthesis and virus-induced hepatitis in vivo. J Immunol. 1983 Sep;131(3):1531–1538. [PubMed] [Google Scholar]
  4. Carl M., Dasch G. A. Characterization of human cytotoxic lymphocytes directed against cells infected with typhus group rickettsiae: evidence for lymphokine activation of effectors. J Immunol. 1986 Apr 1;136(7):2654–2661. [PubMed] [Google Scholar]
  5. Farley M. M., Shafer W. M., Spitznagel J. K. Antimicrobial binding of a radiolabeled cationic neutrophil granule protein. Infect Immun. 1987 Jun;55(6):1536–1539. doi: 10.1128/iai.55.6.1536-1539.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fitzgerald P. A., Mendelsohn M., Lopez C. Human natural killer cells limit replication of herpes simplex virus type 1 in vitro. J Immunol. 1985 Apr;134(4):2666–2672. [PubMed] [Google Scholar]
  7. Froelich C. J., Sibbitt W. L., Jr, Bankhurst A. D. Enrichment of natural killer cells by negative selection: comparison to Percoll gradient separation method. J Immunol Methods. 1983 Nov 25;64(3):327–333. doi: 10.1016/0022-1759(83)90440-4. [DOI] [PubMed] [Google Scholar]
  8. Ganz T., Selsted M. E., Szklarek D., Harwig S. S., Daher K., Bainton D. F., Lehrer R. I. Defensins. Natural peptide antibiotics of human neutrophils. J Clin Invest. 1985 Oct;76(4):1427–1435. doi: 10.1172/JCI112120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Goldfarb R. H. Cell-mediated cytotoxic reactions. Hum Pathol. 1986 Feb;17(2):138–145. doi: 10.1016/s0046-8177(86)80286-6. [DOI] [PubMed] [Google Scholar]
  10. Greaves M. F., Brown G. Purification of human T and B lymphocytes. J Immunol. 1974 Jan;112(1):420–423. [PubMed] [Google Scholar]
  11. Grimm E. A., Mazumder A., Zhang H. Z., Rosenberg S. A. Lymphokine-activated killer cell phenomenon. Lysis of natural killer-resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes. J Exp Med. 1982 Jun 1;155(6):1823–1841. doi: 10.1084/jem.155.6.1823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hatcher F. M., Kuhn R. E. Destruction of Trypanosoma cruzi by Natural killer cells. Science. 1982 Oct 15;218(4569):295–296. doi: 10.1126/science.6812218. [DOI] [PubMed] [Google Scholar]
  13. Hauser W. E., Jr, Tsai V. Acute toxoplasma infection of mice induces spleen NK cells that are cytotoxic for T. gondii in vitro. J Immunol. 1986 Jan;136(1):313–319. [PubMed] [Google Scholar]
  14. Hercend T., Griffin J. D., Bensussan A., Schmidt R. E., Edson M. A., Brennan A., Murray C., Daley J. F., Schlossman S. F., Ritz J. Generation of monoclonal antibodies to a human natural killer clone. Characterization of two natural killer-associated antigens, NKH1A and NKH2, expressed on subsets of large granular lymphocytes. J Clin Invest. 1985 Mar;75(3):932–943. doi: 10.1172/JCI111794. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hidore M. R., Murphy J. W. Correlation of natural killer cell activity and clearance of Cryptococcus neoformans from mice after adoptive transfer of splenic nylon wool-nonadherent cells. Infect Immun. 1986 Feb;51(2):547–555. doi: 10.1128/iai.51.2.547-555.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hidore M. R., Murphy J. W. Natural cellular resistance of beige mice against Cryptococcus neoformans. J Immunol. 1986 Dec 1;137(11):3624–3631. [PubMed] [Google Scholar]
  17. Lanier L. L., Le A. M., Civin C. I., Loken M. R., Phillips J. H. The relationship of CD16 (Leu-11) and Leu-19 (NKH-1) antigen expression on human peripheral blood NK cells and cytotoxic T lymphocytes. J Immunol. 1986 Jun 15;136(12):4480–4486. [PubMed] [Google Scholar]
  18. Lipscomb M. F., Alvarellos T., Toews G. B., Tompkins R., Evans Z., Koo G., Kumar V. Role of natural killer cells in resistance to Cryptococcus neoformans infections in mice. Am J Pathol. 1987 Aug;128(2):354–361. [PMC free article] [PubMed] [Google Scholar]
  19. Lozzio C. B., Lozzio B. B. Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome. Blood. 1975 Mar;45(3):321–334. [PubMed] [Google Scholar]
  20. Nencioni L., Villa L., Boraschi D., Berti B., Tagliabue A. Natural and antibody-dependent cell-mediated activity against Salmonella typhimurium by peripheral and intestinal lymphoid cells in mice. J Immunol. 1983 Feb;130(2):903–907. [PubMed] [Google Scholar]
  21. Old L. J. Tumor necrosis factor (TNF). Science. 1985 Nov 8;230(4726):630–632. doi: 10.1126/science.2413547. [DOI] [PubMed] [Google Scholar]
  22. Ortaldo J. R., Sharrow S. O., Timonen T., Herberman R. B. Determination of surface antigens on highly purified human NK cells by flow cytometry with monoclonal antibodies. J Immunol. 1981 Dec;127(6):2401–2409. [PubMed] [Google Scholar]
  23. Paetkau V., Bleackley R. C., Riendeau D., Harnish D. G., Holowachuk E. W. Toward the molecular biology of IL-2. Contemp Top Mol Immunol. 1985;10:35–61. doi: 10.1007/978-1-4684-4838-2_2. [DOI] [PubMed] [Google Scholar]
  24. Perussia B., Starr S., Abraham S., Fanning V., Trinchieri G. Human natural killer cells analyzed by B73.1, a monoclonal antibody blocking Fc receptor functions. I. Characterization of the lymphocyte subset reactive with B73.1. J Immunol. 1983 May;130(5):2133–2141. [PubMed] [Google Scholar]
  25. Phillips J. H., Lanier L. L. Dissection of the lymphokine-activated killer phenomenon. Relative contribution of peripheral blood natural killer cells and T lymphocytes to cytolysis. J Exp Med. 1986 Sep 1;164(3):814–825. doi: 10.1084/jem.164.3.814. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Storkus W. J., Dawson J. R. Oxygen-reactive metabolites are not detected at the effector-target interface during natural killing. J Leukoc Biol. 1986 May;39(5):547–557. doi: 10.1002/jlb.39.5.547. [DOI] [PubMed] [Google Scholar]
  27. Tarkkanen J., Saksela E., Lanier L. L. Bacterial activation of human natural killer cells. Characteristics of the activation process and identification of the effector cell. J Immunol. 1986 Oct 15;137(8):2428–2433. [PubMed] [Google Scholar]
  28. Tarkkanen J., Saxén H., Nurminen M., Mäkelä P. H., Saksela E. Bacterial induction of human activated lymphocyte killing and its inhibition by lipopolysaccharide (LPS). J Immunol. 1986 Apr 1;136(7):2662–2669. [PubMed] [Google Scholar]
  29. Timonen T., Ortaldo J. R., Herberman R. B. Analysis by a single cell cytotoxicity assay of natural killer (NK) cells frequencies among human large granular lymphocytes and of the effects of interferon on their activity. J Immunol. 1982 Jun;128(6):2514–2521. [PubMed] [Google Scholar]
  30. Timonen T., Ortaldo J. R., Herberman R. B. Characteristics of human large granular lymphocytes and relationship to natural killer and K cells. J Exp Med. 1981 Mar 1;153(3):569–582. doi: 10.1084/jem.153.3.569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Timonen T., Saksela E. Isolation of human NK cells by density gradient centrifugation. J Immunol Methods. 1980;36(3-4):285–291. doi: 10.1016/0022-1759(80)90133-7. [DOI] [PubMed] [Google Scholar]
  32. Trinchieri G., Perussia B. Human natural killer cells: biologic and pathologic aspects. Lab Invest. 1984 May;50(5):489–513. [PubMed] [Google Scholar]
  33. Weiss J., Victor M., Elsbach P. Role of charge and hydrophobic interactions in the action of the bactericidal/permeability-increasing protein of neutrophils on gram-negative bacteria. J Clin Invest. 1983 Mar;71(3):540–549. doi: 10.1172/JCI110798. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Young J. D., Hengartner H., Podack E. R., Cohn Z. A. Purification and characterization of a cytolytic pore-forming protein from granules of cloned lymphocytes with natural killer activity. Cell. 1986 Mar 28;44(6):849–859. doi: 10.1016/0092-8674(86)90007-3. [DOI] [PubMed] [Google Scholar]
  35. Zehavi-Willner T., Berke G. The mitogenic activity of staphylococcal enterotoxin B (SEB): a monovalent T cell mitogen that stimulates cytolytic T lymphocytes but cannot mediate their lytic interaction. J Immunol. 1986 Oct 15;137(8):2682–2687. [PubMed] [Google Scholar]

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