Relevance of mast cells and hepatic lobule innervation to liver injury.

Chronic liver diseases commonly result in liver fibrosis, and eventually liver cirrhosis. In the last decade, a new theory explaining liver fibrosis has been established. Accordingly, the development of liver fibrosis due to chronic liver diseases is thought to be mediated by inflammatory cells. They release fibrogenic mediators such as transforming growth factors (TGF)-beta, which are considered to be responsible for the activation and transformation of fat-storing cells. Recently, the involvement of mast cells and peripheral and autonomic nervous system in the fibrogenesis has been suggested. This study was aimed to establish the presence and distribution of mast cells and nerve fibers in the rat liver in the light of their implication in liver inflammatory and fibrotic disorders. Mast cells and afferent (sensory) fibers were detected immunohistochemically. An immunofluorescent method was applied to demonstrate tryptase and serotonin (SER) in the mast cells, while the primary sensory neuronal processes were identified by using antibodies against their marker calcitonin gene-related peptide (CGRP) and the proinflammatory mediator substance P (SP). The portal tracts and fibrous septa contained numerous mast cells, which exhibited strong immuno-reactivity to tryptase and SER. SER-positive nerve fibers were also found. It is generally accepted that no nerve fibers are present in the hepatic lobules, but the current investigation clearly demonstrates availability of CGRP-, SP, and SER-immunoreactive nerve fibers there. Our results indicate that in the rat liver portal tracts and hepatic lobules there are numerous mast cells, sensory and autonomic nerve fibers, which may be involved in liver injury by the inflammatory mediators they release.