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Localization of α 2 ‐macroglobulin protein and messenger RNA in rat liver fibrosis: Evidence for the synthesis of α 2 ‐macroglobulin within Schistosoma mansoni egg granulomas
Author(s) -
Tiggelman A M,
Boers W,
Moorman A F,
de Boer P A J,
Van der Loos C M,
Rotmans J P,
Chamuleau R A
Publication year - 1996
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510230547
Subject(s) - messenger rna , granuloma , in situ hybridization , biology , parenchyma , hepatic stellate cell , pathology , protein biosynthesis , fibrosis , microbiology and biotechnology , macroglobulin , proteases , immunology , endocrinology , gene , biochemistry , enzyme , medicine
Abstract α 2 ‐Macroglobulin (α 2 M) in the rat is a strong‐reacting acute‐phase protein with potent protease‐inhibiting and cytokine‐binding properties. Production of α 2 M is ascribed mainly to liver parenchymal cells. In the present study, we investigated, by means of immunohistochemistry and in situ hybridization, whether fibrosis in the rat liver induced by Schistosoma mansoni eggs leads to local production of α 2 M. α 2 M protein and messenger RNA (mRNA) in the unaffected liver tissue, as well as serum values of α 2 M, were comparable in control rats and egg‐injected rats, at 1, 3, and 8 weeks after injection of the eggs. α 2 M was homogeneously distributed across the liver lobule. In contrast, at the sites of the granulomas, a strong increase in α 2 M was observed. α 2 M mRNA was expressed by granuloma cells, but not by the surrounding liver parenchymal cells. Within the granulomas, α 2 M protein was present in numerous spindle‐shaped cells and was diffusely distributed in the extra‐cellular matrix. Using double‐staining techniques, a subpopulation of the α 2 M‐positive cells in the granulomas appeared to be desmin‐positive, suggesting a myofibroblast origin. In addition, parenchymal cells directly surrounding the granulomas contained α 2 M protein in approximately 50% of the granulomas 1 week after injection of the eggs. In situ hybridization on consecutive sections revealed that these parenchymal cells showed only background activity of α 2 M mRNA, suggesting uptake of α 2 M‐protein by these parenchymal cells and previous activation of α 2 M by proteases within the granuloma. The significance of the present study is that α 2 M is produced locally at sites of inflammation and liver fibrosis, without measurable increase of serum levels of α 2 M. Unexpectedly, α 2 M present at the sites of the granulomas is not produced by the liver parenchymal cells, but rather by granuloma cells.