Localization of α2-macroglobulin protein and messenger RNA in rat liver fibrosis: Evidence for the synthesis of α2-macroglobulin within Schistosoma mansoni egg granulomas

✍ Scribed by A M Tiggelman; W Boers; A F Moorman; P A J de Boer; C M Van der Loos; J P Rotmans; R A Chamuleau

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 888 KB
• Volume: 23
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.510230547

✦ Synopsis

fibrosis, without measurable increase of serum levels of a 2 -Macroglobulin (a 2 M) in the rat is a strong-reacting a 2 M. Unexpectedly, a 2 M present at the sites of the granuacute-phase protein with potent protease-inhibiting and lomas is not produced by the liver parenchymal cells, cytokine-binding properties. Production of a 2 M is asbut rather by granuloma cells. (HEPATOLOGY 1996; cribed mainly to liver parenchymal cells. In the present 23:1260-1267.) study, we investigated, by means of immunohistochemistry and in situ hybridization, whether fibrosis in the rat liver induced by Schistosoma mansoni eggs leads to a 2 -Macroglobulin (a 2 M) is a strong-reacting acutelocal production of a 2 M. a 2 M protein and messenger phase protein in the rat, reaching up to 100-fold its RNA (mRNA) in the unaffected liver tissue, as well as basal concentration in plasma during an acute-phase serum values of a 2 M, were comparable in control rats reaction (APR). 1 a 2 M is the major proteinase inhibitor and egg-injected rats, at 1, 3, and 8 weeks after injection of the eggs. a 2 M was homogeneously distributed across in humans and rats, blocking a wide spectrum of prothe liver lobule. In contrast, at the sites of the granuloteinases-regardless of their substrate specificity and mas, a strong increase in a 2 M was observed. a 2 M mRNA catalytic mechanisms-by means of sterical entrapwas expressed by granuloma cells, but not by the ment and covalent binding of the proteinase. 2,3 Interacsurrounding liver parenchymal cells. Within the granution of a 2 M with proteinases induces a conformational lomas, a 2 M protein was present in numerous spindlechange of a 2 M, and subsequent receptor-mediated shaped cells and was diffusely distributed in the extraclearance of a 2 M mainly by liver parenchymal cellular matrix. Using double-staining techniques, a cells. 2,[4][5][6] The conformational change induced by ensubpopulation of the a 2 M-positive cells in the granulotrapping a protease allows a 2 M to bind cytokines like mas appeared to be desmin-positive, suggesting a myofitransforming growth factor b (TGF-b) and platelet-debroblast origin. In addition, parenchymal cells directly surrounding the granulomas contained a 2 M protein in rived growth factor, 2,6,7 thereby inhibiting 8-10 or promotapproximately 50% of the granulomas 1 week after injecing 11,12 the effects of these cytokines, probably detion of the eggs. In situ hybridization on consecutive pending on the type of cell involved. sections revealed that these parenchymal cells showed During APR, liver parenchymal cells account for the only background activity of a 2 M mRNA, suggesting uplarge increase of a 2 M in serum, as demonstrated by a take of a 2 M-protein by these parenchymal cells and prestrong increase in the expression of a 2 M messenger vious activation of a 2 M by proteases within the granu-RNA (mRNA) and protein in situ, 13 and as supported loma. The significance of the present study is that a 2 M by numerous studies on a 2 M production by parenchyis produced locally at sites of inflammation and liver mal cells in vitro. 1,6,14 In addition, rat fat-storing cells (FSCs) in culture have also been shown to produce, secrete, and endocytose a 2 M.