Publication: Ultrastructural localization of integrin subunits
α
α
3 and
α
α
6 in capillarized sinusoids of the human cirrhotic liver
Authors
Quondamatteo, F. ; Kempkensteffen, C. ; Miosge, N. ; Sonnenberg, A. ; Herken, R.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Normal liver sinusoids are not lined by a
basement membrane (BM). In contrast, in the course of
development of liver cirrhosis, a structured BM is
formed de novo in the space of Disse. This BM
contributes to the inhibition of the metabolic function of
the liver but the pathogenic background of the formation
of this perisinusoidal BM is still unclear. Integrins of the
ß1-class are generally essential for BM stability and
some of them (such as
α
2ß1,
α
3ß1 and
α
6ß1) appear de
novo in the perisinusoidal space of the cirrhotic liver.
Their cellular distribution in capillarized sinusoids as
well as the correlation between their cellular distribution
and the formation of the microvascular BM in the
cirrhotic liver has not been shown at the ultrastructural
level. In the present work we aimed to clarify this issue.
We
focused on integrins
α
3ß1 and
α
6ß1 and localised
them ultrastructurally in human cirrhotic liver
microvessels using postembedding immunogold which
allows the ultrastructural localization of antigens with
high resolution in the tissue. The newly formed
basement membrane of capillarized sinusoids was
visualized by means of fixation with addition of tannic
acid, which enables the visualization of structures of the
extracellular matrix with the highest resolution. Also, we
carried out laminin detection using postembedding
immunogold. Our results show that both
α
3ß1 and
α
6ß1
are expressed on the surface of both hepatocytes and
endothelial cells, i.e. on both sides of the newly formed
basement membrane. This latter shows zones of higher
density both in close proximity to the endothelial and to
the hepatocytic surfaces which resemble laminae densae.
We
propose that hepatocytes and endothelial cells may,
therefore, by expressing such integrins, contribute to the
formation of this pathological BM in the microvessels of
the human cirrhotic liver. On stellate cells, which are
major producers of BM components, both integrins
α
3ß1 and
α
6ß1 were also localized.
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