Possible Existence of a Novel Amphipathic Immunostimulator in the Phenol-Water Extracts of Mycobacteriaceae

Takako Ikeda-Fujita, Shozo Kotani, Masachika Tsujimoto, Tomohiko Ogawa, Ichiro Takahashi, Haruhiko Takada, Hidetoshi Shimauchi, Shigeki Nagao, Susumu Kokeguchi, Keiiiro Kato, Ikuya Yano, Haruki Okamura, Toshishide Tamura, Kazuhiro Harada, Hiroko Usaml, Akihiko Yamamoto, Shigenori Tanaka, Yoshiko Kato

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Abstract

The extracts having diverse immunostimulating activities were obtained as a water-phase fraction from four bacterial species representing the 4 genera (Mycobacterium, Nocardia, Gordona, and Rhodococcus) of Mycobacteriaceae by the phenol-water method, which is commonly used for extraction of endotoxic lipopolysaccharides (LPS) from gram-negative bacteria and amphipathic substances from gram-positives. These fractions, especially those of G. aurantiaca and R. terrae, showed strong stimulatory effects on murine splenocytes, macrophages of mice and guinea pigs, the immunoadjuvant activities in guinea pigs and mice, and the distinct activities inducing a tumor necrosis factor and interferons α/β and γ in primed mice. The fractions from G. aurantiaca and R. terrae exhibited potent pyrogenicity and the ability to activate the clotting enzyme cascade of the horseshoe crab (Tachypleus tridentatus). Some of these biological activities were not very different from the potency of the reference endotoxic LPS derived from Escherichia coli or Fusobacterium nucleatum. But the test fractions neither showed the activity to prepare rabbit skin to the local Shwartzman reaction, nor reacted with anti-lipid A conventional and monoclonal antibodies. Furthermore, unlike LPS, these fractions stimulated the splenocytes of C3H/HeJ mice (LPS-Nonresponder). Although the fractions showing the above biological activities have not yet been adequately purified, they contained poly-saccharides, whose main constituent sugar is mannose with a smaller amount of arabinose, fatty acids consisting primarily of palmitic, stearic, and tuberculostearic acids, and small amounts of peptides and amino sugars. Since components characteristic of known immunomodulators of bacterial origin, namely endotoxins (lipid A‘s), cell wall peptidoglycans, lipoteichoic acids, cord factors (trehalose dimycolates), or deoxyribonucleic acids, were practically not detected in these fractions, the agent responsible for the above bioactivities is considered to be a novel substance different from the known, bacterial immunomodulators.

Original languageEnglish
Pages (from-to)289-311
Number of pages23
JournalMICROBIOLOGY and IMMUNOLOGY
Volume31
Issue number4
DOIs
Publication statusPublished - Jan 1 1987

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ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Virology

Cite this

Ikeda-Fujita, T., Kotani, S., Tsujimoto, M., Ogawa, T., Takahashi, I., Takada, H., Shimauchi, H., Nagao, S., Kokeguchi, S., Kato, K., Yano, I., Okamura, H., Tamura, T., Harada, K., Usaml, H., Yamamoto, A., Tanaka, S., & Kato, Y. (1987). Possible Existence of a Novel Amphipathic Immunostimulator in the Phenol-Water Extracts of Mycobacteriaceae. MICROBIOLOGY and IMMUNOLOGY, 31(4), 289-311. https://doi.org/10.1111/j.1348-0421.1987.tb03091.x