A novel costimulatory factor for gamma interferon induction found in the livers of mice causes endotoxic shock

Author:

Okamura H1,Nagata K1,Komatsu T1,Tanimoto T1,Nukata Y1,Tanabe F1,Akita K1,Torigoe K1,Okura T1,Fukuda S1

Affiliation:

1. Department of Bacteriology, Hyogo College of Medicine, Nishinomiya, Japan.

Abstract

Administration of monoclonal anti-CD3 antibody to mice treated with Propionibacterium acnes induced secretion of a high level of gamma interferon (IFN-gamma) into the circulation system, while it induced no significant release in untreated mice. In order to analyze this high-level induction of IFN-gamma in these bacterium-treated mice, we investigated the factors that might be involved. An activity that induces IFN-gamma in T cells was observed in the liver extracts of mice treated with P. acnes and subsequently challenged with lipopolysaccharide. Here, we purified an IFN-gamma-inducing factor from the liver extract to homogeneity and characterized it. Its molecular mass was 18 to 19 kDa, and its pI was 4.9. The amino acid sequence of the NH2-terminal portion was determined and shown to have no similarities to any protein in the EMBL, GenBank, and PIR data bases. The same molecule was also demonstrated in the serum factor that was previously reported to have an IFN-gamma-inducing activity and to have an apparent molecular mass of 75 kDa. Moreover, the activity of this serum factor was recovered in the fraction containing the 18- to 19-kDa protein under reducing conditions and was shown to have the same NH2-terminal amino acid sequence as that of the factor from the liver extract. In addition to the ability to induce IFN-gamma, this protein augmented T-cell proliferation and NK activity in the spleen cells. Thus, several of its biological activities were apparently similar to those of interleukin-12. These results indicated that this novel protein, which exhibited marked costimulatory activity on IFN-gamma production in vitro, was elevated vivo in response to P. acnes treatment. This factor, probably released from the producing cells by lipopolysaccharide stimuli, may be involved in the high-level induction of IFN-gamma in the P. acnes-treated mice.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Immunology,Microbiology,Parasitology

Reference26 articles.

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3. Natural killer (NK) cells as responder to interleukin 2 (IL-2). II. IL-2- induced interferonproduction;Handa K.;J. Immunol.,1983

4. Interferonis a mediator of lethal lipopolysaccharide-induced Schwartzman-like shock reactions in mice;Heremans H.;J. Exp. Med.,1990

5. Role of IFN-~ producing NK cells in the lethal endotoxin-induced generalized Schwartzman reaction in mice;Heremans H.;J. Interferon Res.,1991

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