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  • 1
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary An experimental model of schistosomal portal fibrosis is described. Sepharose beads the size of schistosome eggs, loaded or not with soluble egg antigen (SEA) fromSchistosoma mansoni, are injected into the coecal vein of C3H/Sn mice and become embolized in the liver. Only SEA-coated beads evoke a granulomatous reaction; this is enhanced by simultaneous priming of the mice with spleen cells fromSchistosoma mansoni-infected syngeneic animals. The fibrosis, which ensues around the beads, is stable and is much more evident after priming. Preliminary collagen tissue immunotyping reveals the presence of collagen deposits of types I and III collagen. Type IV collagen remains unchanged in the portal tracts. The model appears to be well suited for studies of the pathogenesis of portal fibrosis.
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  • 2
    ISSN: 1432-0878
    Keywords: Key words Fibrosis ; Transforming growth factor-β ; Basement membranes ; Heparan sulphate proteoglycans ; Schistosoma mansoni ; Mouse (Swiss OF1)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  In an attempt to elucidate further the immunopathological pathways that underlie fibrogenesis induced by Schistosoma mansoni, we have studied the distribution of basement membrane compounds, heparan sulphate proteoglycans (HSPG) and the fibrogenic cytokine transforming growth factor (TGF)-β in two models of experimental schistosomiasis mansoni (experimental murine infection and synchronous granulomas induced by injection of egg-antigen-coupled beads into the caecal vein). Deposition of the basement membrane proteins type IV collagen, laminin and entactin in schistosomal granulomas was seen 3 days after the implantation of egg-antigen-coupled beads in the liver and persisted over time (32 days). Up-regulation of the membrane-bound HSPG syndecan-1 was observed in the schistosomal granuloma. These syndecan-1-immunoreactive cells represented a distinct subpopulation of granuloma cells; they were different from both mature, unstimulated B-cells (CD40-positive) and endothelial cells (CD105-positive). Deposition of the matrix HSPG perlecan within the granuloma was most prominent 8–16 days after injection. TGF-β expression was observed in acute (8 weeks) and chronically (13 weeks) infected mice, mainly at the periphery of the schistosomal granuloma and on Kupffer cells in the liver parenchyma. From these observations, we infer that schistosomal fibrosis is composed of various groups of matrix components and that TGF-β, which is secreted by granuloma cells, is one of the fibrogenic mediators in schistosomal fibrogenesis.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Cell & tissue research 32 (1943), S. 545-556 
    ISSN: 1432-0878
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Cell & tissue research 32 (1943), S. 557-586 
    ISSN: 1432-0878
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Zusammenfassung Mit Hilfe neu entwickelter Methodik wurden erstmalig differenzierte Gewebezellen verschiedenster Herkunft dreidimensional vermessen und für jede einzelne Zelle das Kernvolumen, das Plasmavolumen und die sich aus diesen ergebende Kern-Plasma-Relation bestimmt. Für die Kerne konnte das bekannte Verdoppelungsgesetz von Jakobj erneut bestätigt werden, darüber hinaus auch das Vorkommen von Zwischenklassen bei der Leber des Frosches, beim Epithel des Plexus chorioideus, bei den Spermiocyten I. Ordnung und beim Amnionepithel des Menschen nachgewiesen werden. Beim Darmepithel der Maus, dem Pleuraepithel des Meerschweinchens und dem Endothel der vorderen Augenkammer des Rindes trat nur eine Kernklasse auf. Beim hungernden Frosch stellte sich gegenüber einem gut ernährten Frosch in den Leberzellen neben einer Verringerung des Plasmavolumens auch eine solche der Kernvolumina ein, und zwar in dem Maße, daß die Kern-Plasma-Relation konstant und die gleiche blieb. Das Auftreten einer konstanten Kern-Plasma-Relation wurde für die Leberzellen eines gut ernährten wie eines hungernden Frosches, für das Darmepithel der Maus, das Pleuraepithel vom Meerschweinchen, das Epithel des Plexus chorioideus und das Amnion, sowie für die Spermiocyten I. Ordnung vom Menschen nachgewiesen. Für das Endothel der vorderen Augenkammer des Rindes ergab sich eine inkonstante Relation. Der Grad der Konstanz wurde durch die Größe des Korrelationskoeffizienten aus Kern- und Plasmavolumina zum Ausdruck gebracht und somit zahlenmäßig erfaßt. Die bei Konstanz der Kern-Plasma-Relation notwendige Erwartung, daß bei Auftreten von Verdoppelungs- und Zwischenklassen der Kernvolumina sich auch solche der Plasmavolumina ergeben müssen, konnte messend bestätigt werden.
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  • 5
    ISSN: 1432-1955
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract In the present study the kinetics of the uptake and deposition of the major circulating cathodic antigen (CCA) ofSchistosoma mansoni in liver, spleen, and kidney ofS. mansoni infected Swiss mice was investigated in relation to the duration of infection and infection dose (50, 100, 200 cercariae). The presence of antigen was studied with a direct immunofluorescence reaction on frozen sections of the mouse organs, using a fluorescein isothiocyanate (FITC)-labelled mouse IgM monoclonal antibody recognizing a repeating epitope of CCA. CCA was demonstrable from 2 weeks post infection (p.i.) onwards in Kupffer cells in the liver, from 3–4 weeks p.i. onwards in macrophages in the marginal zones in the spleen and from 8 weeks p.i. onwards in kidney glomeruli. The immunofluorescence reactions on CCA in kidney glomeruli, however, remained relatively weak.
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  • 6
    ISSN: 1432-1955
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The clearance of schistosome-specific model immune complexes (IC) consisting of circulating anodic antigen (CAA), a gut-associated excretory-secretory antigen, and radiolabeled monoclonal antibody (IgG1) was investigated in mice with a light and heavy Schistosoma mansoni infection and in noninfected control animals. The size analysis of the in vitro prepared and injected IC, as determined by density gradient centrifugation, revealed a wide peak at 11S. In infected animals the injected IC were cleared at a significantly lower rate than in control mice. This was attributed to a decreased uptake of IC by the liver in infected mice. In heavily infected mice, 30 min after injection of 11S IC, 8S, 11S, and 〉11S IC were present in the serum, whereas only small 8S IC were detected in the serum of lightly infected animals and noninfected controls. Immune complexes were also present in the serum of heavily infected mice 30 min after injection of antibody and were detectable as 11S and 〉11S IC. The importance of this study is twofold. First, these results show that schistosome-specific monoclonal antibodies can be used in the production of model immune complexes applicable in clearance studies. Second, our findings might be of importance when the possible pathogenicity of circulating IC in schistosomiasis is considered.
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  • 7
    ISSN: 1432-1955
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We developed a method for avoiding contamination by fibroblasts when cultures of peritoneal cells are initiated. Macrophages were identified by immunogold detection [light microscope, transmission (TEM) and scanning (SEM) electron microscopes] of membrane antigens (Mac-1+, Thy-1,2−), non-specific esterase activity and ultrastructural features (TEM). As compared with controls, the yield of peritoneal macrophages was 2- and 12-fold higher, respectively, in acutely and chronically infected mice. In all, 30 “chronic”, 18 “acute” and 18 control cultures were followed up. At a given cell-density seeding, the decline of control, “acute” and “chronic” cultures starts at about day 10, 15, and 27, respectively. In “chronic” cultures only, fibroblast-like cells appear from day 6 onwards; their number increases with time. Cells showing characters intermediary between macrophages and fibroblasts were observed. We suggest that fibroblast-like cells result from the in vitro transdifferentiation of a limited number of in vivo committed macrophages.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Parasitology research 84 (1998), S. 276-280 
    ISSN: 1432-1955
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Adhesion molecules constitute essential elements in inflammation, mediating various cellular interactions. We investigated the expression of adhesion molecules mediating cell-cell [intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1)] and cell-matrix interactions [very late antigen-4 (VLA-4), VLA-6, and syndecan-1] in intestinal granulomas of mice infected with the parasite Schistosoma mansoni. Up-regulation of ICAM-1, LFA-1, and VLA-4 was seen in ileal and colonic granulomas, at both the acute (8 weeks postinfection) and the chronic stage (13–16 weeks postinfection). Up-regulation of VLA-6 was absent in all intestinal granulomas. Syndecan-1 immunoreactive (antigen-driven) B-lymphocytes were seen in the proximity of egg-antigen-laden macrophages in the inner part of ileal and colonic granulomas, although B-cells are considered to be absent in ileal granulomas. Estimation of intestinal granuloma volumes demonstrated the lack of down-modulation observed in ileal granulomas. From our results we infer that adhesion molecules constitute important elements in schistosomal intestinal granuloma formation. Organ-related differences between hepatic and intestinal granulomas exist (e.g., granuloma volume), but these differences are not morphologically reflected in a differential expression of the adhesion molecules ICAM-1, LFA-1, and VLA-4. Syndecan-1 immunoreactive B-lymphocytes also appear to be involved in ileal granuloma formation.
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  • 9
    ISSN: 1432-1955
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract In this study the excretory system ofSchistosoma mansoni was ultrastructurally examined with a recently described monoclonal antibody (mAb) against a circulating antigen. In previous studies this mAb was found to have affinity for the excretory system. Strong immunoreactivity was found on the flagella of the flame cells and of the collecting ducts throughout the worm. The eggshell and the space between the miracidium and the eggshell showed strong reactivity with a declining gradient towards the exterior, suggesting a secretion process. In cercariae, immunoreactivity was restricted to the tegument, whereas in schistosomula the labeling pattern resembled that of the adult worm, demonstrating positive reactivity of the flame cells and no immunostaining of the tegument. This stage-dependent differential expression of different antigens in the excretory system and in the tegument could suggest a maturation process of the excretory system.
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  • 10
    ISSN: 1432-1955
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract To further investigate the factors involved in the modulation of the schistosomal granuloma, mice were primed with immunogenic carbohydrates which were common to soluble egg antigen (SEA) and adult worm antigen. Mice sensitized with LewisX trisaccharide or lacto-N-fucopentaose-III (LNFP-III) displayed an increased cellular response towards SEA-coupled beads implanted in the liver by mesenteric injection, resulting in the formation of larger periparticular granulomas. When animals were sensitized with bovine serum albumin or a structurally related carbohydrate, an accelerated response was not seen. Since LNFP-III is built up of LewisX molecules, and LewisX carbohydrates are common to SEA and worm antigens such as the gut-secreted antigens CCA and CAA (two antigens that could prime egg-antigen-induced granuloma formation), this may explain why adult, live Schistosoma mansoni worms positively modulate egg-antigen-induced hepatic granuloma formation in the murine host. These observations provide new insights into the role of carbohydrates in parasite-host immunity and may yield important implications for choosing worm-derived antigens for the development of anti-schistosome vaccines.
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