Abstract
We investigated whether recombinant human granulocyte colony-stimulating factor (rhG-CSF) en hanced the cytotoxicity of PSK-induced polymorphonuclear leukocytes (PMNs) in the peritoneal cavity. Male C3H/He mice, 8- to 10-week-old, received single subcutaneous (s.c.) or intraperitoneal (i.p.) injection of 2.5 µg/animal of rhG-CSF at different time points before or after an i.p. administration of PSK. In other experiments, mice were s.c. or i.p. treated with the same dosage of rhG-CSF every day for 7 or 14 consecutive days and i.p. injected with 2.5 mg/animal of PSK on the last day. Peritoneal PMNs were harvested 6 hrs after the administration of PSK and purified to more than 95% by Ficoll-Paque for in vitro cytotoxic assay.In vitro cytotoxic assays with51Cr labeled MM46 mammary carcinoma cells were added with 5–20 µg/ml of Nocardia rubra cell wall skeleton (N-CWS) at the beginning of the assay to augment the cytotoxic activity of PMNs.In vitro addition of rhG-CSF to the assay did not enhance the cytotoxicity of PSK-induced PMNs. However, the cytotoxicity was signifi cantly increased when rhG-CSF was s.c. administered 12 hrs before a PSK injection or 2 or 5 hrs after that. On the other hand, the cytotoxicity was rather weak when mice s.c. or i.p. received consecutive injections of rhG-CSF. This cytotoxicity may be mediated by H2O2, since H2O2 production of PMNs during the cytotoxic assay appears to correlate with the levels of cytotoxicity under suppressed H2O2 generation by catalase or enhanced generation by rhG-CSF. These results suggest that rhG-CSF augments the cytotoxicity of PSK-induced PMNs when administeredin vivo timely.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- E/T:
-
effector/target ratio
- i.p.:
-
intraperitoneal (ly)
- N-CWS:
-
Nocardia rubra cell wall skeleton
- PMNs:
-
polymorphonuclear leukocytes
- rhG-CSF:
-
recombinant human granulocyte colony stimulating factor
- s.c.:
-
subcutaneous (ly)
References
Tsukagoshi S, Ohashi F. Protein bound polysaccharide preparation, PSK, effective against mouse sarcoma-180 and rat ascites hepatoma AH-13 by oral use. Jpn J Cancer Res 1974; 65: 557–8.
Akiyama J, Kawamura T, Gotohda E et al. Immuno chemotherapy of transplanted KMT-17 tumor in WKA rats by combination of cyclophosphamide and immuno stimulatory protein-bound polysaccharide isolated from Basidiomycetes. Cancer Res 1977; 37: 3042–5.
Kondo T, Sakamoto J, Ichihashi H et al. Effect of alternating administration of PSK and carbazilqinone in tumor-bearing mice. Jpn J Cancer Res 1981; 72: 293–9.
Tsuru S, Nomoto K. Effects of PSK on specific tumor immunity to syngeneic tumor cells. J Clin Lab Immunol 1983; 4: 215–9.
Kano T, Kumashiro R, Tamada R et al. Late results of postoperative long term cancer chemotherapy for advanced carcinoma of the stomach. Jpn J Surgery 1981; 11: 291–6.
Ohno R, Yamada K, Masaoka T et al. A randomized trial of chemoimmunotherapy of acute nonlymphocytic leukemia in adults using a protein-bound polysaccharide preparation. Cancer Immunol Immunother 1984; 18: 149–54.
Torisu M, Hayashi Y, Ishimitsu T et al. Significant prolongation of disease-free period gained by oral polysaccharide K(PSK) administration after curative surgical operation of colorectal cancer. Cancer Immunol Immunother 1990; 31: 261–8.
Ehrke MJ, Reino JM, Eppolito C et al. The effect of PSK, a protein bound polysaccharide, on immune responses against allogeneic antigens. Int J Immunopharmac 1983; 5: 35–42.
Kato H, Yokoe N, Takemura S et al. Effect of a protein-bound polysaccharide PSK on the complement system. Res Exp Med 1983; 182: 85–94.
Takeichi N, Ba D, Suzuki K et al. Immunological analysis of various immunopotentiators in spontaneously hypertensive rats (SHR) with congenital T-cell depression. In: Yamamura Y, Kotani S eds: Immunomodulation by microbial products and related synthetic compounds. Amsterdam, Excerpta Medica, 1982: 403–6.
Kitani H, Tsuru M, Oguchi M et al. Effect of PSK on interferon production in tumor-bearing mice. J Clin Lab Immunol 1984; 15: 211–4.
Clark RA, Klebanoff SJ. Neutrophil-mediated tumor cell cytotoxicity: Role of the peroxidase system. J Exp Med 1975; 141: 1442–7.
Fisher B, Saffer EA. Tumor cell cytotoxicity by granulocytes from peripheral blood of tumor-bearing mice. J Natl Cancer Inst 1978; 60: 687–91.
Gerrard TL, Cohen DJ, Kaplan AM. Human neutrophilmediated cytotoxicity to tumor cells. J Natl Cancer Inst 1981; 66: 483–8.
Morikawa K, Takeda R, Yamazaki M et al. Induction of tumoricidal activity of polymorphonuclear leukocytes by a linear β-1,3-D-glucan and other immunomodulators in murine cells. Cancer Res 1985; 45: 1496–501.
Morikawa K, Kamegaya S, Yamazaki M et al. Hydrogen peroxide as a tumoricidal mediator of murine polymorphonuclear leukocytes induced by a linearβ-1,3-D glucan and some other immunomodulators. Cancer Res 1985; 45: 3482–6.
Kato H, Kin R, Yamamura Y et al. Tumor inhibitory effect of polymorphonuclear leukocytes (PMN) induced by PSK in the peritoneal cavity of tumor-bearing mice. J Kyoto Pref Univ Med 1987; 96: 927–37.
Azuma I, Taniyama T, Yamazaki M et al. Adjuvant and antitumor activities of Nocardia rubra cell-wall skeletons. Jpn J Cancer Res 1976; 67: 733–6.
Kato H, Yamamura Y, Inoue M et al. In vitro augmentation of cytotoxicity by N-CWS in peritoneal polymorphonuclear leukocytes (PMNs) induced by PSK, OK-432 or N-CWS. Biotherapy 1992; 4: 69–73.
Kondo M, Kato H, Yamamura Y et al. Role of polymorphonuclear leukocytes (PMNs) in the treatment of malignant ascites by intraperitoneal injection of biological response modifiers (BRMs). In: Torisu M, Yoshida T eds: New horizons of tumor immunotherapy. Amsterdam, Elsevier, 1989: 61–78.
Souza LM, Boone TC, Gabrilove J et al. Recombinant human granulocyte colony-stimulating factor: Effects on normal and leukemic myeloid cells. Science 1986; 232: 61–5.
Pick E, Keisari Y: A simple colorimetric method for the measurement of hydrogen peroxide produced by cells in culture. J Immunol Meth 1980; 38: 161–70.
Kato H, Yamamura Y, Kin R et al. Treatment of malignant ascites and pleurisy by a streptococcal preparation OK-432 with fresh frozen plasma - A mechanism of polymorphonuclear leukocytes (PMN) accumulation. Int J Immunopharmac 1989; 11: 117–28.
Torisu M, Katano M, Kimura Y et al. New approach to management of malignant ascites with a streptococcal preparation, OK-432. I. Improvement of host immunityand prolongation of survival. Surgery 1983; 93: 357–64.
Kato H, Inoue M, Yamamura Y et al. Mechanisms of polymorphonuclear leukocytes (PMN) accumulation examined using inhibitors of complement and arachidonic acid cascade in rats treated with OK-432. Nat Immun Cell Growth Regul 1989; 8: 290–300.
Wang JM, Chen ZG, Colella S et al. Chemotactic activity of recombinant human granulocyte colony-stimulating factor. Blood 1988; 72: 1456–60.
Kimura S, Inoue T, Yamashita T et al. Production of factor(s) that render polymorphonuclear leukocytes cytostatic from spleen cells stimulated with a streptococcal preparation, OK-432. Cancer Res 1987; 47: 6204–9.
Shalby MR, Aggarwal BB, Rinderknecht E et al. Activation of human polymorphonuclear neutrophil function by interferon-y and tumor necrosis factor. J Immunol 1985; 135: 2069–73.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kato, H., Inoue, M., Yamamura, Y. et al. Effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on cytotoxicity of PSK-induced peritoneal polymorphonuclear leukocytes (PMNs). Biotherapy 5, 177–186 (1992). https://doi.org/10.1007/BF02171050
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02171050