Skip to main content
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1990 Jan;81(1):69–78. doi: 10.1111/j.1349-7006.1990.tb02509.x

Enhancement of Polymorphonuclear Leukocyte‐mediated Tumor Cytotoxicity by Serum Factor(s)

Akemi Araki 1, Tomio Inoue 1, Seishi Kimura 2, Shigeru Fukase 2, Fujiro Sendo 1,
PMCID: PMC5917947  PMID: 2108949

ABSTRACT

It has been reported that β‐1,3‐d‐glucan isolated from Alcaligenes faecalis (TAK) promoted tumor cytolysis by mouse polymorphonuclear leukocytes (PMN). We investigated the effect of serum on mouse PMN tumor cytolysis induced by TAK and other PMN stimulators. Addition of fetal calf serum (FCS) to the cytolysis assay enhanced tumor cytolysis by PMN in a dose‐dependent manner. Sera obtained from horses, mice, and rats were also effective enhancers of PMN tumor cytolysis. When FCS was added after the assay was under way, the enhancing effect decreased proportionally to the time elapsed. The enhancing activity was detected over a broad range of fractions with a peak at 170 kD by fractionation on a Superose 6 column. The responsible factor(s) in serum was stable after treatment at 60°C, 30 min or after lowering the pH to 2. Mouse PMN stimulated with TAK increased production of hydrogen peroxide in the presence of FCS.

Keywords: Polymorphonuclear leukocytes, Tumor cytotoxicity, Serum factor(s)

Full Text

The Full Text of this article is available as a PDF (554.7 KB).

REFERENCES

  • 1. ) Morikawa , K. , Takeda , R. , Yamazaki , M. and Mizuno , D.Induction of tumoricidal activity of polymorphonuclear leukocytes by a linear β‐1,3‐d‐glucan and other immunomodulators in murine cells . Cancer Res. , 45 , 1496 – 1501 ( 1985. ). [PubMed] [Google Scholar]
  • 2. ) Lichtenstein , A. K. , Kahle , J. , Berek , J. and Zighelboim , J.Successful immunotherapy with intraperitoneal Corynebacterium parvum in a murine ovarian cancer model is associated with the recruitment of tumor lytic neutrophils into the peritoneal cavity . J. Immunol. , 133 , 519 – 526 ( 1984. ). [PubMed] [Google Scholar]
  • 3. ) Lichtenstein , A. K. , Berek , J. , Kahle , J. and Zighelboim , J.Role of inflammatory neutrophils in antitumor effects induced by intraperitoneal administration of Corynebacterium parvum in mice . Cancer Res. , 44 , 5118 – 5123 ( 1984. ). [PubMed] [Google Scholar]
  • 4. ) Morikawa , K. , Kamegaya , S. , Yamazaki , M. and Mizuno , D.Hydrogen peroxide as a tumoricidal mediator of murine polymorphonuclear leukocytes induced by a linear β‐1,3‐d‐glucan and some other immunomodulators . Cancer Res. , 45 , 3482 – 3486 ( 1985. ). [PubMed] [Google Scholar]
  • 5. ) Lichtenstein , A. and Kahle , J.Anti‐tumor effect of inflammatory neutrophils: characteristics of in vivo generation and in vitro tumor cell lysis . Int. J. Cancer , 35 , 121 – 127 ( 1985. ). [DOI] [PubMed] [Google Scholar]
  • 6. ) Hayashi , T. , Arai , S. and Sendo , F.The mechanisms of cytotoxicity to tumor cells by polymorphonuclear leukocytes stimulated with cytokines . Jpn. J. Cancer Res. , 79 , 375 – 383 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7. ) Van Oss , C. J. , Gillman , C. F. , Bronson , P. M. and Border , J. R.Phagocytosis‐inhibiting properties of human serum alpha‐1 acid glycoprotein . Immunol. Commun. , 3 , 321 – 328 ( 1974. ). [DOI] [PubMed] [Google Scholar]
  • 8. ) Costello , M. J. , Gewurz , H. and Siege , J.Inhibition of neutrophil activation by α1‐acid glycoprotein . Clin. Exp. Immunol. , 55 , 465 – 472 ( 1984. ). [PMC free article] [PubMed] [Google Scholar]
  • 9. ) Fisher , B. and Saffer , E. A.Tumor cell cytotoxicity by granulocytes from peripheral blood of tumor‐bearing mice . J. Natl. Cancer Inst. , 60 , 687 – 691 ( 1978. ). [DOI] [PubMed] [Google Scholar]
  • 10. ) Maderazo , E. G. , Anton , T. F. and Ward , P. A.Serum‐associated inhibition of leukotaxis in human with cancer . Clin. Immunol. Immunopathol. , 9 , 166 – 176 ( 1978. ). [DOI] [PubMed] [Google Scholar]
  • 11. ) Patrone , F. , Dallegri , F. , Gremmo , A. , Bonvini , E. , Migliorini , P. , Cantarella , S. , Ferrarini , M. and Sacchetti , C.Serum‐associated inhibition of neutrophil Fc receptors in cancer patients . J. Natl. Cancer Inst. , 67 , 803 – 807 ( 1981. ). [PubMed] [Google Scholar]
  • 12. ) Sedgwick , A. D. , Mackay , A. R. , Bates , M. B. and Willoughby , D. A.The role of plasma factors in the adherence of leukocytes to vascular endothelial cells . J. Pathol. , 140 , 9 – 16 ( 1983. ). [DOI] [PubMed] [Google Scholar]
  • 13. ) Iscove , N. N. and Melchers , F.Complete replacement of serum by albumin, transferrin, and soybean lipid in cultures of lipopolysaccharide‐reactive B lymphocytes . J. Exp. Med. , 147 , 923 – 933 ( 1978. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14. ) Hanson , D. F. , Murphy , P. A. and Windle , B. E.Failure of rabbit neutrophils to secrete endogenous pyrogen when stimulated with staphylococci . J. Exp. Med. , 151 , 1360 – 1371 ( 1980. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15. ) Goto , S. , Nakamura , S. , Goto , K. and Yoshinaga , M.Production of a lymphocyte proliferation potentiating factor by purified polymorphonuclear leukocytes from mice and rabbits . Immunology , 53 , 683 – 692 ( 1984. ). [PMC free article] [PubMed] [Google Scholar]
  • 16. ) Fukase , S. , Inoue , T. , Arai , S. and Sendo , F.Tumor cytotoxicity of polymorphonuclear leukocytes in beige mice: linkage of high responsiveness to linear β‐1,3‐d‐glucan with the beige gene . Cancer Res. , 47 , 4842 – 4847 ( 1987. ). [PubMed] [Google Scholar]
  • 17. ) Pick , E. and Keisari , Y.A simple colorimetric method for the measurement of hydrogen peroxide produced by cells in culture . J. Immunol. Methods , 38 , 161 – 170 ( 1980. ). [DOI] [PubMed] [Google Scholar]
  • 18. ) Araki , Y. , Kurata , S. , Oikawa , T. , Yamashita , T. , Hiroi , M. , Naiki , M. and Sendo , F.A monoclonal antibody reacting with the zona pellucida of the oviductal egg but not with that of the ovarian egg of the golden hamster . J. Reprod. Immunol. , 11 , 193 – 208 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 19. ) Sakai , Y. , Araki , Y. , Yamashita , T. , Kurata , S. , Oikawa , T. , Hiroi , M. and Sendo , F.Inhibition of in vitro fertilization by a monoclonal antibody reacting with the zona pellucida of the oviductal egg but not with that of the ovarian egg of the golden hamster . J. Reprod. Immunol. , 14 , 177 – 189 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 20. ) Kimura , S. , Inoue , T. , Yamashita , T. , Midorikawa , Y. , Arai , S. and Sendo , F.Production of factor(s) that render polymorphonuclear leukocytes cytostatic from spleen cells stimulated with a streptococcal preparation, OK‐432 . Cancer Res. , 47 , 6204 – 6209 ( 1987. ). [PubMed] [Google Scholar]
  • 21. ) Inoue , T. , Hamuro , J. , Yoshimoto , R. , Okano , A. , Shitara , A. , Arai , S. and Sendo , F.A T cell leukemia line produces factor(s) that render rat neutrophils cytotoxic . Jpn. J. Cancer Res. , 77 , 693 – 702 ( 1986. ). [PubMed] [Google Scholar]
  • 22. ) Inoue , T. and Sendo , F.In vitro induction of cytotoxic polymorphonuclear leukocytes by supernatant from a concanavalin A‐stimulated spleen cell culture . J. Immunol. , 131 , 2508 – 2514 ( 1983. ). [PubMed] [Google Scholar]
  • 23. ) Chapman , H. A. , Jr. and Hibbs , J. B. , Jr.Modulation of macrophage tumoricidal capability by components of normal serum: a central role for lipid . Science , 197 , 282 – 285 ( 1977. ). [DOI] [PubMed] [Google Scholar]
  • 24. ) Gerberick , G. F. , Willoughby J. B. , and Willoughby , W. F.Serum factor requirement for reactive oxygen intermediate release by rabbit alveolar macrophages . J. Exp. Med. , 161 , 392 – 408 ( 1985. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25. ) Leonard , E. J. and Skeel , A.Functional differences between resident and exudate peritoneal mouse macrophages: specific serum protein requirements for responsiveness to chemotaxins . J. Reticuloendothel. Soc. , 28 , 437 – 447 ( 1980. ). [PubMed] [Google Scholar]
  • 26. ) Johnston , R. B. , Godzik , C. A. and Cohn , Z. A.Increased superoxide anion production by immunologically activated and chemically elicited macrophages . J. Exp. Med. , 148 , 115 – 127 ( 1978. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27. ) Bianco , C. , Eden , A. and Cohn , Z. A.The induction of macrophage spreading: role of coagulation factors and the complement system . J. Exp. Med. , 144 , 1531 – 1544 ( 1976. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28. ) Spagnuolo , P. J. , Lederman , M. M. , Schiltx , J. , Ellner , J. and Culp , L.A possible role for cold insoluble globulin in chemotactic factor mediated polymorphonuclear leukocyte adherence to plastic . Biochem. Biophys. Res. Commun. , 106 , 471 – 478 ( 1982. ). [DOI] [PubMed] [Google Scholar]
  • 29. ) Vercellotti , G. M. , McCarthy , J. , Furcht , L. T. , Jacob , H. S. and Moldow , C. F.Inflamed fibronectin: an altered fibronectin enhances neutrophil adhesion . Blood , 62 , 1063 – 1069 ( 1983. ). [PubMed] [Google Scholar]
  • 30. ) Hsuech , W. , Jordan , H. H. , Harrison , H. H. and Cobb , M. A.Serum and plasma stimulate prostaglandin production by alveolar macrophages . Prostaglandin , 25 , 793 – 808 ( 1983. ). [DOI] [PubMed] [Google Scholar]
  • 31. ) Araki , A. , Inoue , T. , Kimura , S. and Sendo , F.Modulation by serum factor(s) of neutrophil tumor cytotoxicity . Proc. Jpn. Cancer Assoc., 46th Annu. Meet. , 321 ( 1987. ) ( in Japanese ).
  • 32. ) Lichtenstein , A. , Ganz , T. , Selsted , M. E. and Lehrer , R. I.In vitro tumor cell cytolysis mediated by peptide defensins of human and rabbit granulocytes . Blood , 68 , 1407 – 1410 ( 1986. ). [PubMed] [Google Scholar]

Articles from Japanese Journal of Cancer Research : Gann are provided here courtesy of Wiley

RESOURCES