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A strict requirement for LBP in the TNF hyper-response of Propionibacterium acnes-sensitized mice to LPS

Max Planck Institut fur Immunbiologie, Freiburg, Germany

M. Gumenscheimer

Max Planck Institut fur Immunbiologie, Freiburg, Germany

R. Jack

Institut fur Immunologie und Transfusionsmedizin, Ernst-Moritz-Arndt Universität Greifswald, Greifswald, Germany

T. Merlin

Max Planck Institut fur Immunbiologie, Freiburg, Germany

C. Schütt

Institut fur Immunologie und Transfusionsmedizin, Ernst-Moritz-Arndt Universität Greifswald, Greifswald, Germany

C. Galanos

Max Planck Institut fur Immunbiologie, Freiburg, Germany

One important feature of the Propionibacterium acnes-induced hypersensitivity to LPS is the enhanced production of TNF induced in the sensitized mice upon LPS challenge [Katschinski T., Galanos G., Coumbos A., Freudenberg M.A. Gamma interferon mediates Propionibacterium acnes-induced hypersensitivity to lipopolysaccharide in mice. Infect Immun 1992; 60: 1994-2001]. We investigated the role of LPS binding protein (LBP) in the TNF response of normal and P. acnes-sensitized mice to LPS in LBP+/+ and LBP-/- mice. Treatment of LBP+/+ (BalbC and 129 Sv) mice with P. acnes enhanced their TNF response to LPS by 75-200-fold compared to the non-treated controls. Unsensitized LBP-/- (129 Sv x BalbC) mice were also stimulated by LPS to produce low amounts of TNF. These were enhanced by prior P. acnes treatment, however, only by a factor of 4. The characteristic TNF hyper-response was absent suggesting that the enhanced activity of LPS in sensitized mice is expressed only in the presence of LBP. Evidence for this was obtained by showing that administration of exogenous LBP restored fully the inducibility of the TNF hyper-response in P. acnes-sensitized LBP-/- mice. Their response to LPS was 1000-fold higher then that of sensitized controls without LBP. A similar LBP treatment of unsensitized LBP-/- mice increased the TNF response by a factor of only 5. In an analogous experiment, also IFN--sensitized LBP-/- mice exhibited a TNF overproduction in response to LPS only in the presence of exogenous LBP.

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