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Untersuchungen über die immunbiologische Bedeutung löslicher Leberproteine

Studies of the immunbiologic importance of soluble hepatic proteins

  • Published:
Zeitschrift für die gesamte experimentelle Medizin einschließlich experimentelle Chirurgie

Summary

For antibodies to mitochondria and microsomes of human and rat liver, kidney and thyroid there was no species- and organspecificity. One part of the antibodies reacted specifically with soluble proteins of human or rat liver tested by different serological methods. The characterization of the soluble hepatic proteins was attempted by ultracentrifugation, gelfiltration and ammoniumsulfate precipitation. The organlinked protein was found to remain in the supernatant at 150000 G of liver homogenates and in the first and second peak after gelfiltration on Sephadex G 100. Upon ammoniumsulfate fractionation most of the activity was precipitated at 45% saturation. It was possible to induce specific immuntolerance to organlinked human or rat hepatic proteins neonatal as well as in adult rabbits. The disturbance of the induced tolerances was possible by altered, not by the nativ proteins. The proteins were altered by coupling to chemically defined haptens (sulfanilic acid) and by heating.

The results provide the possibility to study antigendependent inductions of autoimmunity against hepatic proteins under defined conditions.

Zusammenfassung

Antikörper gegen Mitochondrien- und Mikrosomenfraktionen aus Leber, Niere und Schilddrüse von Mensch und Ratte sind komplett species- und organunspezifisch. Antikörper gegen entsprechende lösliche Proteine der Leber sind unter Anwendung verschiedener serologischer Techniken zum Teil als organ- und im untersuchten Bereich auch als speciesspezifisch anzusprechen. Eine nähere Charakterisierung der löslichen Proteinfraktion gelang mittels Ultrazentrifugation, Chromatographie und Ammoniumsulfatfällung. Die organgebundenen Proteine waren im 150000 G Überstand einer Ultrazentrifugation kernfreier Leberhomogenate enthalten. Chromatographisch fanden sich die Proteine im I. und II. Gipfel einer Gelfiltration an Sephadex G 100. Der Hauptteil dieser Fraktionen ließ sich mit Ammoniumsulfat in 45%iger Anreicherung fällen. Gegen so gewonnene lösliche Leberproteine von Mensch und Ratte waren im Kaninchen neonatal und im Erwachsenenalter unter Beachtung bestimmter Dosiszonen Immuntoleranzen induzierbar. Die erzeugten Toleranzen ließen sich nicht mit nativen, jedoch hitzealterierten und an Sulfanilsäure gekoppelten Proteinen durchbrechen.

Die Versuche bieten die Möglichkeit, antigenbedingte Induktionen einer Autoimmunität gegenüber löslichen Leberproteinen unter definierten Bedingungen zu studieren.

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Mit Unterstützung durch die Deutsche Forschungsgemeinschaft.

Theodor Frerichs-Preis 1968.

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Meyer zum Büschenfelde, K.H. Untersuchungen über die immunbiologische Bedeutung löslicher Leberproteine. Z. Gesamte Exp. Med. 148, 131–163 (1968). https://doi.org/10.1007/BF02044245

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