Klinische Wochenschrift

, Volume 59, Issue 14, pp 767–779 | Cite as

Connective tissue components of the normal and fibrotic liver

I. Structure, local distribution and metabolism of connective tissue components in the normal liver and changes in chronic liver diseases
  • J. Rauterberg
  • B. Voss
  • G. Pott
  • U. Gerlach
Übersichten

Summary

The first part of this review describes the chemistry, the occurrence and the metabolism of extracellular connective tissue components in the liver. The normal liver contains typical connective tissue proteins (collagens, structural glycoproteins and proteoglycans) not only in vessel walls, perivascular areas and in the capsule, but they occur also in small amounts in the parenchyma, mainly in the space of Disse along the sinusoidal walls.

The “interstitial” collagens type I and III represent the major amount of collagen in the normal as well as in the fibrotic liver, showing a relative increase of type III in fibrosis. Basement membrane collagens type IV and V as well as the cysteine-rich collagenous components “7 S collagen” and “short chain collagen” have been shown to occur in extracts prepared after limited pepsin digestion. In the normal liver, basement membrane collagen can hardly be detected within the parenchyma by immunofluorescence microscopy; increased occurrence, however, can be shown along the sinusoids even in early stages of chronic liver diseases.

The glycoprotein fibronectin was shown to be distributed very similarly to collagens type I and III, whereas the basement membrane specific glycoprotein laminin is restricted to vessel walls and the epithelial layer of bile ductuli in the normal liver but is also found in the parenchyma in fibrosis.

Occurrence of proteoglycans is increased in fibrosis: a change in the composition of glycosaminoglycans from mainly heparan sulfate in the normal to dermatan- and chondroitin sulfate in the fibrotic liver was observed.

It is not yet clear which cell type is mainly responsible for increased connective tissue synthesis in fibrosis. The occurrence of cells resembling smooth muscle cells (“myofibroblasts”) in connective tissue septa of fibrotic livers and the fact that similar cells which actively synthesize collagen grow from explants of fibrotic livers may indicate the significance of this cell type in the process of liver fibrosis.

Key words

Connective tissue Collagen metabolism Structural glycoproteins Liver fibrosis 

Das Bindegewebe der normalen und fibrotischen menschlichen Leber

I. Struktur, lokale Verteilung und Stoffwechsel des Bindegewebes in der normalen Leber und Änderungen bei chronischen Leberkrankheiten

Zusammenfassung

Im ersten Teil dieser Übersicht werden die Chemie, das Vorkommen im Gewebe und der Stoffwechsel bindegewebstypischer extrazellulärer Komponenten in der Leber beschrieben. Die normale Leber enthält Proteine des Bindegewebes (Kollagene, Struktur-Glykoproteine, Proteoglykane) nicht nur in den Gefäßwänden, den perivasculären Bereichen und in der Kapsel, sondern sie sind auch im Parenchym in geringer Menge, vor allem im Disse'schen Raum entlang den Sinusoiden nachweisbar.

Die „interstitiellen“ Kollagentypen I und III bilden die Hauptmenge des Kollagens sowohl in der normalen als auch in der fibrotischen Leber; dabei ist der relative Anteil an Typ III in der fibrotischen gegenüber der normalen Leber erhöht. Die „Basalmembrankollagene“ Type IV und V sowie die cysteinreichen kollagenen Komponenten 7 S und das Kurzkettenkollagen (Intimenkollagen) konnten aus nach limitiertem Pepsinabbau gewonnenen Extrakten isoliert werden. In der normalen Leber sind die Basalmembrankollagene im Parenchym immunhistologisch kaum nachzuweisen; ein verstärktes Auftreten entlang der Sinusoide ist jedoch schon in frühen Stadien chronischer Lebererkrankungen sichtbar.

Das extrazelluläre Glykoprotein Fibronectin tritt in der Leber in einer dem Typ I und III Kollagen sehr ähnlichen Verteilung auf, während das basalmembranspezifische Glykoprotein Laminin in der nicht-fibrotischen Leber auf Gefäßwände und Gallengangepithelien beschränkt ist und erst bei Fibrose auch in parenchymalen Bereichen nachgewiesen werden kann.

Proteoglykane treten in der fibrotischen Leber ebenfalls vermehrt auf, eine Veränderung der Zusammensetzung der Glykosaminoglykane von überwiegend Heparansulfat in der normalen zu Dermatan-und Chondroitinsulfat in der fibrotischen Leber wurde beobachtet.

Unklarheit besteht noch über den Zelltyp, der hauptsächlich zur vermehrten Bindegewebsbildung in der Leber beiträgt. Vermehrtes Auftreten von Zellen, die glatten Muskelzellen ähneln (Myofibroblasten) in den Septen fibrotischer Lebern und der Befund, daß aus Explantaten fibrotischer Lebern hauptsächlich ähnliche Zellen auswachsen, die eine aktive Kollagensynthese zeigen, können auf die Bedeutung dieses Zelltyps für die Fibrose hindeuten.

Schlüsselwörter

Bindegewebe Kollagenstoffwechsel strukturelle Glykoproteine Leberfibrose 

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Copyright information

© Springer-Verlag 1981

Authors and Affiliations

  • J. Rauterberg
    • 1
  • B. Voss
    • 1
  • G. Pott
    • 1
  • U. Gerlach
    • 1
  1. 1.Institut für Arterioskleroseforschung an der Universität und Medizinische Klinik der Universität MünsterGermany

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