Abstract
Fraction 4 (F4), a protein fraction isolated from aged garlic extract, enhanced cytotoxicity of human peripheral blood lymphocytes (PBL) against both naturalkiller (NK)-sensitive K562 and NK-resistant M14 cell lines. Although F4 treatment alone increased cytotoxicity, the effect was more remarkable when F4 was administered together with suboptimal doses of interleukin-2 (IL-2); combination treatment of 5 μg/ml F4 plus 10 U/ml IL-2 for 72 h generated lymphokine-activated killer activity equivalent to that produced by 100 U/ml IL-2 alone against M14. F4 enhanced IL-2-induced proliferation and IL-2 receptor (Tac) expression of PBL without significant increase of IL-2 production. The enhancement of cytotoxicity both by F4 alone and by F4 plus IL-2 was abolished by anti-IL-2 antibody. F4 also enhanced concanavalin-A(ConA)-induced proliferation of PBL. Radiolabeled-ConA binding assays revealed that F4 treatment greatly augmented the affinity and slightly increased the number of ConA binding sites in PBL. F4 also enhanced ConA-induced IL-2 receptor (Tac) expression and IL-2 production of PBL. Anti-IL-2 antibody inhibited the effect of F4 on ConA-induced proliferation. These data suggest that IL-2 is involved in augmentative effects of F4. Our results indicate that F4 is a very efficient immunopotentiator and may be used for immunotherapy.
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Arima N, Kamio M, Okuma M, Ju G, Uchiyama T (1991) The IL-2 receptor α-chain alters the binding of IL-2 to the β-chain. J Immunol 147:3396
Burnette WN (1981) “Western blotting”: electrophoretic transfer of proteins from sodium dodecyl sulfate-polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A. Anal Biochem 112:195
Bowlin TL, McKown BJ, Kang MS, Sunkara PS (1989) Potentiation of human lymphokine-activated killer cell activity by swainsonine, an inhibitor of glycoprotein processing. Cancer Res 49:4109
Dennis JW (1986) Effects of swainsonine and polyinosinic: polycytidylic acid on murine tumor cell growth and metastasis. Cancer Res 46:5131
Feldman HA (1972) Mathematical theory of complex ligand-binding systems at equilibrium: some methods for parameter fitting. Anal Biochem 48:317
Feldman H, Rodbard D, Levin D (1972) Mathematical theory of cross-reactive radioimmunoassays and ligand-binding systems at equilibrium. Anal Biochem 45:530
Fujiwara M, Nakata T (1967) Induction of tumour immunity with tumour cells treated with extract of garlic (Allium sativum). Nature 216:83
Hirao Y, Sumioka I, Nakagami S, Yamamoto M, Hatono S, Yoshida S, Fuwa T, Nakagawa S (1987) Activation of immunoresponder cells by the protein fraction from garlic extract. Phytother Res 1:161
Itoh K, Shiba K, Shimizu Y, Suzuki R, Kumagai K (1985) Generation of activated killer (AK) cells by recombinant interleukin 2 (rIL 2) in collaboration with interferon-γ (IFN-γ). J Immunol 134: 3124
Jain RC, Konar DB (1978) Effect of garlic oil in experimental cholesterol atherosclerosis. Atherosclerosis 29:125
Lau BHS, Woolley JL, Marsh CL, Barker GR, Koobs DH, Torrey RR (1986) Superiority of intralesional immunotherapy withCorynebacterium parvum andAllium sativum in control of murine transitional cell carcinoma. J Urol 136:703
Owen-Schaub LB, Gutterman JU, Grimm EA (1988) Synergy of tumor necrosis factor and interleukin 2 in the activation of human cytotoxic lymphocytes: effect of tumor necrosis factor α and interleukin 2 in the generation of human lymphokine-activated killer cell cytotoxicity. Cancer Res 48:788
Roberts K, Lotze MT, Rosenberg SA (1987) Separation and functional studies of the human lymphokine-activateddkiller cell. Cancer Res 47:4366
Sumiyoshi H, Wargovich MJ (1990) Chemoprevention of 1,2-dimethylhydrazine-induced colon cancer in mice by naturally occurring organosulfur compounds. Cancer Res 50:5084
Voss SD, Leary TP, Sondel PM, Robb RJ (1993) Identification of a direct interaction between interleukin 2 and the p64 interleukin 2 receptor gamma chain. Proc Natl Acad Sci USA 90:2428
Wall KA, Pierce JD, Elbein AD (1988) Inhibitors of glycoprotein processing alter T-cell proliferative responses to antigen and to interleukin 2. Proc Natl Acad Sci USA 85:5644
Yagita M, Nakajima M, Saksela E (1989) Suppression of human natural killer cell activity by amino sugars. Cell Immunol 122:83
Yamamoto S, Hoon DSB, Chandler P, Schmid I, Irie RF (1990) Generation of lymphokine-activated killer cell activity by low-dose recombinant interleukin-2 and tumor cells. Cell Immunol 128:516
You WC, Blot WJ, Chang YS, Ershow AG, Yang ZT, An Q, Henderson B, Xu GW, Fraumeni JF, Wang TG (1988) Diet and high risk of stomach cancer in Shandong, China. Cancer Res 48:3518
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Morioka, N., Sze, L.L., Morton, D.L. et al. A protein fraction from aged garlic extract enhances cytotoxicity and proliferation of human lymphocytes mediated by interleukin-2 and concanavalin A. Cancer Immunol Immunother 37, 316–322 (1993). https://doi.org/10.1007/BF01518454
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DOI: https://doi.org/10.1007/BF01518454