Immunohistochemical study of intrahepatic innervation
in man
D. Tiniakos1, A.D. Burt2,
Chr. Kittas1
1Laboratory of Histology and
Embryology, Medical School University of Athens, Greece
2Department of Pathology, Royal
Victoria Infirmary, Medical School University of Newcastle upon
Tyne, U.K.
Introduction-Aim: Physiological studies have shown that
intrahepatic nerves may have important metabolic, sensory and
motor functions. The ontogenesis of intrinsic human liver innervation
has not been studied in detail before and little is known about
the distribution and nature of peptidergic nerves in adult liver.
Material and Methods: Normal human liver tissue from 14
foetuses and 10 adults was used in this study. Nerve fibers were
identified in paraffin sections using immunohistochemical methods
and a panel of antibodies to pan-neural markers (NSE, S100, chromogranin,
PGP 9.5) and neuropeptides (NPY, somatostatin, galanin, CGRP).
Results: In human foetal liver, a neural network was
established in the portal tracts at 20 weeks of gestation. The
density of nerve fibres reached adult levels at 32nd-33rd week.
Rare intra-acinar nerves appeared at 28 weeks and were restricted
in the periportal areas. The peptidergic neural supply was abundant
and diverse. Galaninergic and somatostatinergic fibers were noted
in portal tracts from 22 weeks but were not identified in any
of the adult livers. CGRP-positive fibers were noted in portal
tracts from 32 weeks onwards. No intrasinusoidal peptidergic nerves
could be identified. In human adult liver, a dense neural supply
was observed in portal tracts and the acini, where intrasinusoidal
nerves were most abundant in zone 1. Peptidergic innervation was
characterized by NPY-ergic nerve fibers, which may belong to the
extensive efferent sympathetic neural network observed in the
mammalian liver.
Conclusions: Human foetal liver at 20 weeks of gestation
is characterized by an intrinsic neural network distributed in
portal tracts. The density of nerve fibers increases progressively
towards term. Developmentally-regulated expression of galanin
and somatostatin may play a role in liver morphogenesis. In adult
liver, the presence of nerve fibers in portal tracts may play
a role in blood haemodynamics and the direct innervation of hepatocyôes
may be related to the control of metabolic functions. Alterations
in the distribution of intrahepatic nerves may contribute to the
metabolic and haemodynamic disturbances which characterize chronic
liver disease in man.
Key words: Human, liver, innervation, immunohistochemistry.
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