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2011 | 14 | 3 |

Tytuł artykułu

Influence of bestatin, an inhibitor of aminopeptidases, on T and B lymphocyte subsets in mice

Treść / Zawartość

Warianty tytułu

Języki publikacji

EN

Abstrakty

EN
Bestatin, a low-molecular weight dipeptide, is a potent inhibitor of aminopeptidase N which has been demonstrated to have antitumor and immunomodulatory effects. The effects of bestatin (10, 1 and 0.1mg/kg) administered intraperitoneally once, five or ten times to mice on the total number of lymphocytes in the thymus, spleen and mesenteric lymph nodes and the percentage and the absolute number of T cell subsets (CD4+CD8+, CD4-CD8-, CD4+, CD8+) in the thymus and T (CD3+, CD4+, CD8+) and B (CD19+) lymphocytes in the spleen and mesenteric lymph nodes were studied. It has been found that bestatin administered ten times at doses of 10, 1 and 0.1 mg/kg increased the total number of thymocytes, splenocytes and lymphocytes of mesenteric lymph nodes. Bestatin also changed the percentage and the absolute number of T cell subsets in the thymus and T and B lymphocytes in the peripheral lymphatic organs. Five and ten exposures to bestatin (10, 1 and 0.1 mg/kg) increased the absolute count of both immature CD4+CD8+ and CD4-CD8- thymic cells. Moreover, both a single and multiple administration of bestatin (1 and 0.1 mg/kg) decreased the percentage and absolute count of CD3+ splenocytes and mesenteric lymph node cells with corresponding decreases in the percentage and absolute count of CD4+ and CD8+ cells. Both a single and multiple administration of bestatin at all the doses under investigation augmented the percentage and the absolute count of CD19+ (B lymphocytes) in the peripheral lymphatic organs. The results of the study show that there is a relationship between the effect induced by bestatin and the dose of the drug as well as the number of doses applied. The strongest effect on the T and B lymphocyte subsets was noted after five injections of bestatin at doses of 1 and 0.1 mg/kg.

Słowa kluczowe

Wydawca

-

Rocznik

Tom

14

Numer

3

Opis fizyczny

p.393-403,ref.

Twórcy

autor
  • Department of Biochemistry, Pharmacology and Toxicology, Faculty of veterinary Medicine, Wroclaw University of Environmental and Life Sciences, Norwida 31, 50-375 Wroclaw, Poland
autor
autor

Bibliografia

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  • Bauvois B, Dauzonne D (2006) Aminopeptidase-N/CD13 (EC 3.4.11.2.) inhibitors: chemistry, biological evaluations and therapeutic prospects. Med Res Rev 26: 88-130.
  • Dunlap BE, Dunlap SA, Rich DH (1984) Effect of bestatin on in vitro responses of murine lymphocytes to T-cell stimuli. Scand J Immunol 20: 237-245.
  • Favaloro EJ, Browning T, Facey D (1993) CD13 (GP 150; aminopeptidase-N): predominant functional activity in blood is localized to plasma and is not cell-surface associated. Exp Hematol 21: 1695-1701.
  • Hirayama Y, Sakamaki S, Takayanagi N, Tsuji Y, Sagawa T, Chiba H, Matsunaga T, Niitsu Y (2003) Chemotherapy with ubenimex corresponding to patient age and organ disorder for 18 cases of acute myelogeneous leukemia in elderly patients-effects, complications and long-term survival. Gan To Kagaku Ryoho 30: 1113-1118.
  • Ichimura E, Yamada M, Nishikawa K, Abe F, Nakajima T (2006) Immunohistochemical expression of aminopeptidase N (CD13) in human lung squamous cell carcinomas, with special reference to bestatin adjuvant therapy. Pathol Int 56: 296-300.
  • Ichinose Y, Genka K, Koike T, Kato H, Watanabe Y, Mori T, Iioka S, Sakuma A, Ohta M, NK421 Lung Cancer Surgery Group (2003) Randomized double-blind placebo-controlled trial of bestatin in patients with resected stage I squamous-cell lung carcinoma. J Natl Cancer Inst 95: 605-610.
  • Ishizuka M, Masuda T, Kanbayashi N, Fukasawa S, Takeuchi T, Aoyagi T, Umezawa H (1980a) Effect of bestatin on mouse immune system and experimental murine tumors. J Antibiot (Tokyo) 33: 642-652.
  • Ishizuka M, Sato J, Sugiyama Y, Takeuchi T, Umezawa H (1980b) Mitogenic effect of bestatin on lymphocytes. J Antibiot (Tokyo) 33: 653-662.
  • Jarstrand C, Blomgren H (1981) Bestatin, a new immunomodulator, enhances migration and phagocytosis of human granulocytes in vitro. J Clin Lab Immunol 5: 67-69.
  • Jung K, Pergande M, Wischke UW (1984) Characterization of particulate and soluble variants of the brush-border enzymes alanine aminopeptidase, alkaline phosphatase and gamma-glutamyltransferase in human urine. Biomed Biochim Acta 43: 1357-1364.
  • Lkhagvaa B, Tani K, Sato K, Toyoda Y, Suzuka C, Sone S (2008) Bestatin, an inhibitor for aminopeptidases, modulates the production of cytokines and chemokines by activated monocytes and macrophages. Cytokine 44: 386-391.
  • Look AT, Ashmun RA, Shapiro LH, Peiper SC (1989) Human myeloid plasma membrane glycoprotein CD 13 (gp150) is identical to aminopeptidase N. J Clin Invest 83: 1299-1307.
  • Luan Y, Xu W (2007) The structure and main functions of aminopeptidase N. Curr Med Chem 14: 639-647.
  • Morikawa K, Morikawa S, Nakano A, Oseko F (1989) Bestatin, an inhibitor of aminopeptidase B, suppresses the proliferation and differentiation of human B-cells in vitro. Int J Immunopharmacol 11: 905-913.
  • Nelson BH, Willerford DM (1998) Biology of the interleukin-2 receptor. Adv Immunol 70: 1-81.
  • Ota K, Uzuka Y (1992) Clinical trials of bestatin for leukemia and solid tumors. Biotherapy 4: 205-214.
  • Otsuka T, Okamura S, Ohhara N, Harada M, Hayashi S, Yamaga S, Omori F, Niho Y (1988) Stimulatory effects of bestatin on human B-cell colony formation. Int J Immunopharmacol 10: 587-591.
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  • Shibuya K, Chiba S, Hino M, Kitamura T, Miyagawa K, Takaku F, Miyazano K (1991) Enhancing effect of ubenimex (bestatin) on proliferation and differentiation of hematopoietic progenitor cells, and the suppressive effect on proliferation of leukemic cell lines via peptidase regulation. Biomed Pharmacother 45: 71-80.
  • Suda H, Takita T, Aoyagi T, Umezawa H (1976) The structure of bestatin. J Antibiot (Tokyo) 29: 100-101.
  • Tsukagoshi S (1987) A new antitumor drug with immunomodulating activity, ubenimex (bestatin). Gan To Kagaku Ryoho 14: 2385-2391.
  • Umezawa H, Aoyagi T, Suda H, Hamada M, Takeuchi T (1976) Bestatin, an inhibitor of aminopeptidase B produced by actinomycetes. J Antibiot (Tokyo) 29: 97-99.
  • Urabe A, Mutoh Y, Mizoguchi H, Takaku F, Ogawa N (1993) Ubenimex in the treatment of acute nonlymphocytic leukemia in adults. Ann Hematol 67: 63-66.
  • Wakabayashi Y, Hashimoto M, Saitoh K, Osawa H, Koike M, Hirose S (1991) Effects of bestatin (Ubenimex) on human T-cell colony formation. Anticancer Drugs 2: 39-43.
  • Weissmann N, Leyhausen G, Maidhof H, Tanaka W, Umezawa H, Müller WE (1985) Mitogenic potentials of bestatin, amastatin, arphamenines A and B, FK-156 and FK-565 on spleen lymphocytes. J Antibiot (Tokyo) 38: 772-778.
  • Yamagishi H, Naito K, Ueda Y, Itoi S, Kohnosu H, Kobayashi M, Kubo H., Matsuda A, Oka T (1991) Bestatin administration and the change in cellular immunity. Biomed Pharmacother 45: 117-120.

Typ dokumentu

Bibliografia

Identyfikatory

Identyfikator YADDA

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