Molecular and structural requirements of a lipoteichoic acid from Enterococcus hirae ATCC 9790 for cytokine-inducing, antitumor, and antigenic activities

H. Takada, Y. Kawabata, R. Arakaki, S. Kusumoto, K. Fukase, Y. Suda, T. Yoshimura, Susumu Kokeguchi, K. Kato, T. Komuro, N. Tanaka, M. Saito, T. Yoshida, M. Sato, S. Kotani

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Abstract

Comparison was made between the immunobiological and antigenic properties of two lipoteichoic acid (LTA) fractions (LTA-1 and -2) from Enterococcus hirae ATCC 9790, their glycolipid portions, and synthetic compounds partially mimicking the above bacterial products. The more lipophilic LTA-2 fraction was capable of inducing serum tumor necrosis factor alpha and interleukin-6 in muramyldipeptide-primed mice and serum gamma interferon in those primed with Propionibacterium acnes. The LTA-2 fraction also induced tumor necrosis factor alpha, interleukin-6, and thymocyte-activating factor (essentially interleukin-l) in murine peritoneal macrophage cultures. Consecutive intravenous injections of muramyldipeptide and the LTA-2 fraction in Meth A fibrosarcoma-bearing BALB/c mice caused hemorrhagic necrosis and marked regression leading to complete regression of the tumor with no accompanying weakening or lethal effects. The LTA-2 fraction was at least 10,000-fold less pyrogenic in rabbits than a reference endotoxic lipopolysaccharide. The more hydrophilic LTA-1 fraction, on the other hand, showed at most marginal activity in the in vivo and in vitro assays. Natural glycolipids (NGL-1 and - 2) which were prepared from a chloroform-methanol extract of Streptococcus pyogenes and E. hirae cells, and comparable in structure to the lipid moieties of the LTA-1 and -2 fractions, respectively, were practically inactive in all of the assays. None of the test synthetic compounds was immunobiologically active, although synthetic partial counterparts of the structure of LTA proposed by W. Fischer (Handb. Lipid Res. 6:123-234, 1990) reacted with murine monoclonal antibody TS-2, which was raised against OK- 432, a penicillin-killed S. pyogenes preparation, and capable of neutralizing the cytokine-inducing activities of the LTA-2 fraction.

Original languageEnglish
Pages (from-to)57-65
Number of pages9
JournalInfection and Immunity
Volume63
Issue number1
Publication statusPublished - 1995
Externally publishedYes

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Cytokines
Streptococcus pyogenes
Glycolipids
Interleukin-6
Tumor Necrosis Factor-alpha
lipoteichoic acid
Enterococcus hirae
Picibanil
Lipids
Propionibacterium acnes
Fibrosarcoma
Interleukins
Peritoneal Macrophages
Thymocytes
Chloroform
Serum
Intravenous Injections
Penicillins
Interferon-gamma
Methanol

ASJC Scopus subject areas

  • Immunology

Cite this

Molecular and structural requirements of a lipoteichoic acid from Enterococcus hirae ATCC 9790 for cytokine-inducing, antitumor, and antigenic activities. / Takada, H.; Kawabata, Y.; Arakaki, R.; Kusumoto, S.; Fukase, K.; Suda, Y.; Yoshimura, T.; Kokeguchi, Susumu; Kato, K.; Komuro, T.; Tanaka, N.; Saito, M.; Yoshida, T.; Sato, M.; Kotani, S.

In: Infection and Immunity, Vol. 63, No. 1, 1995, p. 57-65.

Research output: Contribution to journalArticle

Takada, H, Kawabata, Y, Arakaki, R, Kusumoto, S, Fukase, K, Suda, Y, Yoshimura, T, Kokeguchi, S, Kato, K, Komuro, T, Tanaka, N, Saito, M, Yoshida, T, Sato, M & Kotani, S 1995, 'Molecular and structural requirements of a lipoteichoic acid from Enterococcus hirae ATCC 9790 for cytokine-inducing, antitumor, and antigenic activities', Infection and Immunity, vol. 63, no. 1, pp. 57-65.
Takada, H. ; Kawabata, Y. ; Arakaki, R. ; Kusumoto, S. ; Fukase, K. ; Suda, Y. ; Yoshimura, T. ; Kokeguchi, Susumu ; Kato, K. ; Komuro, T. ; Tanaka, N. ; Saito, M. ; Yoshida, T. ; Sato, M. ; Kotani, S. / Molecular and structural requirements of a lipoteichoic acid from Enterococcus hirae ATCC 9790 for cytokine-inducing, antitumor, and antigenic activities. In: Infection and Immunity. 1995 ; Vol. 63, No. 1. pp. 57-65.
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abstract = "Comparison was made between the immunobiological and antigenic properties of two lipoteichoic acid (LTA) fractions (LTA-1 and -2) from Enterococcus hirae ATCC 9790, their glycolipid portions, and synthetic compounds partially mimicking the above bacterial products. The more lipophilic LTA-2 fraction was capable of inducing serum tumor necrosis factor alpha and interleukin-6 in muramyldipeptide-primed mice and serum gamma interferon in those primed with Propionibacterium acnes. The LTA-2 fraction also induced tumor necrosis factor alpha, interleukin-6, and thymocyte-activating factor (essentially interleukin-l) in murine peritoneal macrophage cultures. Consecutive intravenous injections of muramyldipeptide and the LTA-2 fraction in Meth A fibrosarcoma-bearing BALB/c mice caused hemorrhagic necrosis and marked regression leading to complete regression of the tumor with no accompanying weakening or lethal effects. The LTA-2 fraction was at least 10,000-fold less pyrogenic in rabbits than a reference endotoxic lipopolysaccharide. The more hydrophilic LTA-1 fraction, on the other hand, showed at most marginal activity in the in vivo and in vitro assays. Natural glycolipids (NGL-1 and - 2) which were prepared from a chloroform-methanol extract of Streptococcus pyogenes and E. hirae cells, and comparable in structure to the lipid moieties of the LTA-1 and -2 fractions, respectively, were practically inactive in all of the assays. None of the test synthetic compounds was immunobiologically active, although synthetic partial counterparts of the structure of LTA proposed by W. Fischer (Handb. Lipid Res. 6:123-234, 1990) reacted with murine monoclonal antibody TS-2, which was raised against OK- 432, a penicillin-killed S. pyogenes preparation, and capable of neutralizing the cytokine-inducing activities of the LTA-2 fraction.",
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T1 - Molecular and structural requirements of a lipoteichoic acid from Enterococcus hirae ATCC 9790 for cytokine-inducing, antitumor, and antigenic activities

AU - Takada, H.

AU - Kawabata, Y.

AU - Arakaki, R.

AU - Kusumoto, S.

AU - Fukase, K.

AU - Suda, Y.

AU - Yoshimura, T.

AU - Kokeguchi, Susumu

AU - Kato, K.

AU - Komuro, T.

AU - Tanaka, N.

AU - Saito, M.

AU - Yoshida, T.

AU - Sato, M.

AU - Kotani, S.

PY - 1995

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N2 - Comparison was made between the immunobiological and antigenic properties of two lipoteichoic acid (LTA) fractions (LTA-1 and -2) from Enterococcus hirae ATCC 9790, their glycolipid portions, and synthetic compounds partially mimicking the above bacterial products. The more lipophilic LTA-2 fraction was capable of inducing serum tumor necrosis factor alpha and interleukin-6 in muramyldipeptide-primed mice and serum gamma interferon in those primed with Propionibacterium acnes. The LTA-2 fraction also induced tumor necrosis factor alpha, interleukin-6, and thymocyte-activating factor (essentially interleukin-l) in murine peritoneal macrophage cultures. Consecutive intravenous injections of muramyldipeptide and the LTA-2 fraction in Meth A fibrosarcoma-bearing BALB/c mice caused hemorrhagic necrosis and marked regression leading to complete regression of the tumor with no accompanying weakening or lethal effects. The LTA-2 fraction was at least 10,000-fold less pyrogenic in rabbits than a reference endotoxic lipopolysaccharide. The more hydrophilic LTA-1 fraction, on the other hand, showed at most marginal activity in the in vivo and in vitro assays. Natural glycolipids (NGL-1 and - 2) which were prepared from a chloroform-methanol extract of Streptococcus pyogenes and E. hirae cells, and comparable in structure to the lipid moieties of the LTA-1 and -2 fractions, respectively, were practically inactive in all of the assays. None of the test synthetic compounds was immunobiologically active, although synthetic partial counterparts of the structure of LTA proposed by W. Fischer (Handb. Lipid Res. 6:123-234, 1990) reacted with murine monoclonal antibody TS-2, which was raised against OK- 432, a penicillin-killed S. pyogenes preparation, and capable of neutralizing the cytokine-inducing activities of the LTA-2 fraction.

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