Biliary secretion of fluid phase markers is modified under post-cholestatic conditions

Einfluss einer Cholestase auf die Ausscheidung von Fluid-Phase Markern in die Galle

Zusammenfassung

Hepatozyten nehmen Makromoleküle aus dem Blut über Rezeptor-vermittelte oder Fluid-phase-Endozytose auf. Diese Makromoleküle können entweder spezifisch oder unspezifisch durch die Zelle transportiert werden (=Transzytose) und dann in die Galle ausgeschieden werden. Da die Transzytosewege verschiedener Fluid-phase Marker (FPM) kaum charakterisiert sind, wurde die biliäre Sekretion von zwei FPM (Meerrettichperoxidase (HRP), FITC-Dextran) in der isoliert perfundierten Rattenleber untersucht. Nach kurzzeitig Angebot (1 min) wurde HRP biphasisch in die Galle ausgeschieden: miteinem schnellen/frühen (5 min) und einem langsamen/verzögerten (15 min) Sekretionsmaximum. Andere Arbeitsgruppen hatten gezeigt, dass eine durch Gallengangsligatur hervorgerufene Kurzzeitcholestase (BDL) die HRP Sekretion beeinflußt. Daher wurde in dieser Arbeit die Auswirkung einer BDL sowohl auf die Ausscheidung von HRP als auch auf FITC-Dextran untersucht. Obwohl BDL das erste HRP Sekretionsmaximum erhöhte, hatte sie keine Auswirkungen auf das zweite HRP Ausscheidungsmaximum oder auf die Ausscheidung von FITC-Dextran. Perfusion bei niedriger Temperatur (16°C) unter Kontrollbedingungen oder nach BDL blockierte die FITC-Dextran Sekretion und den langsamen HRP Weg, während die schnelle HRP Sekretion in die Galle verzögert wurde und BDL darauf keinen stimulierenden Einfluß mehr hatte. Während der 16°C Perfusion erfolgte eine Aufnahme von HRP und FITC-Dextran in die Hepatozyten, da nach Erwärmen auf 37°C die Marker in die Galle ausgeschieden wurden. Daraus lässt sich schließen, dass BDL die rasche Sekretion von HRP über einen Temperatur-sensitiven transzellulären und/oder parazellulären Weg induziert. Über diesen Weg wird FITC-Dextran nicht transportiert, vielmehr erfolgt die Sekretion von FITC-Dextran in die Galle ausschliesslich über einen transzellulären Weg.

Summary

Hepatocytes take up macromolecules from the circulation by receptor-mediated and/or fluid-phase endocytosis. These molecules are either selectively or nonspecifically transported through the cell (transcytosis) and are subsequently secreted into bile. As transcytosis of diverse fluid-phase markers (FPM) is still poorly characterized, biliary secretion of two FPMs (horseradish peroxidase (HRP), FITC-Dextran) was studied in the isolated perfused rat liver following short-term (1 min) single-pulse administration. HRP was secreted into bile with a fast (5 min) and slow (15 min) transit time, while FITC-dextran appeared in bile in a single peak at 7 min. Short-time reversible cholestasis, induced by bile duct ligation (BDL), had been shown to affect HRP secretion. Here, we compare the influence of 2 h BDL on post-cholestatic biliary secretion of HRP and FITC-dextran. BDL drastically stimulated the fast component of HRP secretion into bile, but had an effect neither on the second HRP peak nor on the appearance of FITC-dextran in bile. Perfusion at low temperature (16°C) under control and post-cholestatic conditions suppressed both, the second HRP peak and the appearance of FITC-dextran in bile, but uptake of FPM by endocytosis was not inhibited as the markers were secreted upon re-warming to 37°C. In addition, perfusion at low temperature under control and post-cholestatic conditions delayed the appearance of the fast HRP peak in bile and it abrogated the stimulating effect of BDL on the first HRP peak. These data indicate that BDL boosts HRP secretion along a temperature-sensitive transcellular pathway and/or a paracellular route. This fast route is taken only by HRP but not by FITC-dextran, the latter being exclusively transported by a transcellular route under all conditions investigated.

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Abbreviations

BDL:

bile duct ligation

KHB:

Krebs-Henseleith bicarbonate buffer

HRP:

horseradish peroxidase

IPL:

isolated perfused liver

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Correspondence to Renate Fuchs.

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Ellinger, I., Fuchs, R. Biliary secretion of fluid phase markers is modified under post-cholestatic conditions. Wien Med Wochenschr 158, 579–582 (2008). https://doi.org/10.1007/s10354-008-0600-5

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Schlüsselwörter

  • Leber
  • Cholestase
  • Gallengangsligatur
  • Transzytose
  • Fluid-Phase Marker

Keywords

  • Liver
  • Cholestasis
  • Bile duct ligation
  • Transcytosis
  • Fluid-phase marker