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. 1987 Sep;25(2):149–152. doi: 10.1007/BF00199956

Depressed natural cytotoxicity but normal natural killer cytotoxic factor (NKCF) production by mononuclear cells derived from patients with hepatocellular carcinoma

Roger H Brookes 1, Michael C Kew 2, Arthur R Rabson 3,
PMCID: PMC11041111  PMID: 2822243

Abstract

This study investigated the relation between the production of natural killer cytotoxic factors (NKCF) and the phenomenon of natural killing (NK) activity against target K562 cells. Two different models of defective NK cell activity were employed. In the first instance, cytotoxic activity of mononuclear cells (MN) derived from patients with hepatocellular carcinoma was compared to the ability of these cells to produce NKCF. Although direct cytotoxicity was considerably impaired in these patients, the ability of their MN to produce NKCF when stimulated with K562 cells was found to be normal. In the second model, MN treated with the lysosomotropic drug monensin showed considerably reduced direct cytotoxic activity, although they were capable of producing normal amounts of NKCF when activated by K562 cells. These results therefore indicate that there is no correlation between NK activity and corresponding NKCF release, and suggest that NKCF production and activity is independent of direct NK cytotoxic activity.

Keywords: Natural Killing, Hepatocellular Carcinoma, Natural Killing Cell, Mononuclear Cell, Cell Activity

References

  • 1.Adams D, Snyderman R. Do macrophages destroy nascent tumors? J Natl Cancer Inst. 1979;63:1341. [PubMed] [Google Scholar]
  • 2.Basu SK, Goldstein JL, Anderson RGW, Brown MS. Monensin interrupts the recycling of low density lipoprotein receptors in human fibroblasts. Cell. 1981;24:493. doi: 10.1016/0092-8674(81)90340-8. [DOI] [PubMed] [Google Scholar]
  • 3.Bonavida B, Wright SC. Role of natural killer cytotoxic factors in the mechanism of target cell killing by natural killer cells. J Clin Immunol. 1986;6:1. doi: 10.1007/BF00915358. [DOI] [PubMed] [Google Scholar]
  • 4.Carpen O, Virtanen I, Saksela E. The cytotoxic activity of human natural killer cells requires an intact secretory apparatus. Cell Immunol. 1981;58:97. doi: 10.1016/0008-8749(81)90152-0. [DOI] [PubMed] [Google Scholar]
  • 5.Farram E, Targan SR. Identification of human natural killer soluble cytotoxic factor(s) derived from NK-enriched lymphocyte populations:specificity of generation and killing. J Immunol. 1983;130:1252. [PubMed] [Google Scholar]
  • 6.Graves SS, Bramhall J, Bonavida B. Studies on the lethal hit stage of natural killer cell-mediated cytotoxicity I. Both phorbol ester and ionophore are required for release of natural killer cytotoxic factors, suggesting a role for protein kinase C activity. J Immunol. 1986;137:1977. [PubMed] [Google Scholar]
  • 7.Herman J, Kew MC, Rabson AR. Defective interleukin-1 production by natural killer cells of patients with cancer. Cancer Immunol Immunother. 1985;19:148. doi: 10.1007/BF00199724. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Herman J, Dinarello CA, Kew MC, Rabson AR. The role of interleukin-1 in tumor NK cell activity in cancer patients by treating target cells with IL-1. J Immunol. 1985;135:2882. [PubMed] [Google Scholar]
  • 9.Hiserodt JC, Britvan IJ, Targan SR. Differential effects of various pharmacologic agents on the cytotoxic reaction mechanism of the human natural killer lymphocyte: further resolution of programming for lysis and NKTL into discrete stages. J Immunol. 1982;129:2266. [PubMed] [Google Scholar]
  • 10.Kaäriäinen L, Hashimoto K, Saraste J, Virtanen I, Penttinen K. Monensin and FCCP inhibit the intracellular transport of alphavirus membrane glycoproteins. J Cell Biol. 1980;87:783. doi: 10.1083/jcb.87.3.783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Kasahara T, Djeu JY, Dougherty SF, Oppenheim JJ. Capacity of human large granular lymphocytes to produce multiple lymphokines: interleukin 2, interferon, and colony-stimulating factor. J Immunol. 1983;131:2379. [PubMed] [Google Scholar]
  • 12.Ortaldo JR, Ranson JR, Sayers TJ, Herberman RB. Analysis of cytostatic/cytotoxic lymphokines: Relationship of natural killer cytotoxic factor to recombinant lymphotoxin, recombinant tumor necrosis factor and leukoregulin. J Immunol. 1986;137:2857. [PubMed] [Google Scholar]
  • 13.Peters PM, Ortaldo JR, Shalaby RM, Svedersky LP, Nedwin GE, Bringman TS, Hass PE, Aggarwal BB, Herberman RB, Goeddel DV, Palladino MA. Natural killer-sensitive targets stimulate production of TNFα but not TNFβ by highly purified human peripheral blood large granular lymphocytes. J Immunol. 1986;137:2592. [PubMed] [Google Scholar]
  • 14.Podack ER, Dennert G. Assembly of two types of tubules with putative cytolytic function by cloned natural killer cells. Nature. 1982;302:442. doi: 10.1038/302442a0. [DOI] [PubMed] [Google Scholar]
  • 15.Roder JC, Kiessling R, Biberfeld P, Anderson K. Target-effector interaction in the natural killer cell system. II The isolation of NK cells and studies on the mechanism of killing. J Immunol. 1978;121:2509. [PubMed] [Google Scholar]
  • 16.Roder JC, Argov S, Klein M, Petersson C, Kiessling R, Anderson K, Hansson M. Target-effector interactions in the natural killer cell system. V. Energy requirements, protein synthesis and the possible involvement of lysosomal enzymes. Immunology. 1980;40:107. [PMC free article] [PubMed] [Google Scholar]
  • 17.Sayers TJ, Ranson JH, Denn AC, Herberman RB, Ortaldo JR. Analysis of a cytostatic lymphokine produced by incubation of lymphocytes with tumor cells: Relationship to leukoregulin and distinction from recombinant lymphotoxin, recombinant tumor necrosis factor and natural killer cytotoxic factor. J Immunol. 1986;137:385. [PubMed] [Google Scholar]
  • 18.Scala G, Allavena P, Djeu JY, Kasahara T, Ortaldo JR, Herberman RB, Oppenheim JJ. Human large granular lymphocytes are potent producers of interleukin-1. Nature. 1984;309:56. doi: 10.1038/309056a0. [DOI] [PubMed] [Google Scholar]
  • 19.Son K, Kew MC, Rabson AR. Role of natural killer cytotoxic factors in the mechanism of target-cell killing by natural killer cells. J Clin Immunol. 1982;6:1. doi: 10.1007/BF00915358. [DOI] [PubMed] [Google Scholar]
  • 20.Tarlakoff AM, Vassalli P. Comparative studies of intracellular transport of secretory proteins. J Cell Biol. 1978;79:694. doi: 10.1083/jcb.79.3.694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Wright SC, Bonavida B. Selective lysis of NK-sensitive cells by a soluble mediator released from murine spleen cells and human peripheral blood lymphocytes. J Immunol. 1981;126:1516. [PubMed] [Google Scholar]
  • 22.Wright SC, Bonavida B. Studies of mechanism of natural killer cell-mediated cytotoxicity. V. Lack of NK specificity of the level of induction of natural killer cytotoxic factors in cultures of human, murine, or rat effector cells stimulated with mycoplasma-free cell lines. J Immunol. 1984;133:3415. [PubMed] [Google Scholar]
  • 23.Young JD, Hengartner H, Podack ER, Cohn ZA. Purification and characterisation of cytolytic pore-forming protein from granules of cloned lymphocytes with natural killer activity. Cell. 1986;44:849. doi: 10.1016/0092-8674(86)90007-3. [DOI] [PubMed] [Google Scholar]

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