Cell-matrix interactions in Schistosomal portal fibrosis: a dynamic event

Abstract

In recent years, one of the most significant progress in the understanding of liver diseases was the demonstration that liver fibrosis is a dynamic process resulting from a balance between synthesis and degradation of several matrix components, collagen in particular. Thus, fibrosis has been found to be a very early event during liver diseases, be it of toxic, viral or parasitic origin, and to be spontaneously reversible, either partially or totally. In liver fibrosis cell matrix interactions are dependent on the existence of the many factors (sometimes acting in combination) which produce the same events at the cellular and molecular levels. These events are: (i) the recruitment of fiber-producing cells, (ii) their proliferation, (iii) the secretion of matrix constituents of the extracellular matrix, and (iv) the remodeling and degradation of the newly formed matrix. All these events represent, at least in principle, a target for a therapeutic intervention aimed at influencing the experimentally induced hepatic fibrosis. In this context, hepatosplenic schistosomiasis is of particular interest, being an immune cell-mediated granulomatous disease and a model of liver fibrosis allowing extensive studies in human and animals as well as providing original in vitro models.

Immunopathology of Schistosoma mansoni infection

“…They reacted with antibodies from chronically infected mice and were named major serologic antigens MSA1, MSA2, and MSA3 (221). The highly purified MSA1, a glycoprotein with an estimated molecular size of 138 kDa, was specific for the egg stage and could be used as an immunodiagnostic reagent with sera of heavily infected humans (143,222 (38,116,146,229,291) and occurs mostly at the site of the resolving granulomatous reactions. However, fibrous bands also appear around portal veins distant from granulomas.…”

“…At least two different cell types initiate hepatic granuloma fibrosis in humans: fibroblasts and the smooth-muscle cells that dedifferentiate to myofibroblasts (146). It appears that both host immune and parasite factors are involved in triggering fibroblast activation and collagen synthesis (Table 3).…”

Hepatic stellate cells and parasite-induced liver fibrosis

“…Four stages have been suggested in the process of fibrosis in schistosomiasis. These are: recruitment of fibroblasts and/or differentiation of HSC; proliferation of the HSC; secretion of ECM molecules; and ECM remodelling [21]. In chronic schistosomiasis, the rate of collagen accumulation decreases and a change in the type of collagen accumulated can occur from type 1 to type 3 as demonstrated in mice infected with S. japonicum [22] .…”

The therapeutic effect of the neuropeptide hormone somatostatin on Schistosoma mansoni caused liver fibrosis

“…During periovular granuloma formation fibronectin produced by macrophages is deposited around the inflammatory cells [8,9] composing a large part of the extracellular matrix. This is followed by the deposition of the proteoglycans dermatan sulphate, to a lesser extent heparan sulphate [10], and the interstitial collagen types I & III that all together form the fibrotic tissue.…”