Browsing by Subject "Granuloma"

Now showing 1 - 3 of 3
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    A human in vitro granuloma model for the investigation of multinucleated giant cell and granuloma formation
    (Murcia : F. Hernández, 2001) Seitzer, U.; Haas, H.; Gerdes, J.
    A method for the in vitro generation of granulomas and its use in the analysis of the human granulomatous response is summarized. As a target for the cellular response L3 larvae of Nippostrongylus brasiliensis are coincubated with human mononuclear blood cells, and within seven to fourteen days the development of blood monocytes to mature macrophages and to epithelioid cells and multinucleated giant cells (MGC) as typical constituents of granulomas clustered around the nematode is observed. The following review describes the uses and applications of this model for phenotyping, functional, formation and modulating studies of granulomas and MGCs, taking into account its unique features compared to other in vitro models. With respect to MGC formation, procedures are described and examples are given which allow the phenotyping of these cells using immunofluorescence and immunohistological techniques. In addition, the potential of this model for illuminating functional aspects of MGC is described applying an isolation protocol for MGC and a subsequent reverse-transcriptase polymerase chain reaction method for the analysis of single cells. Moreover, the significance and relevance of using this granuloma model is discussed in the follow up analysis of in vivo findings of interleukin-6 expression in MGC of granulomas of patients with sarcoidosis. These in vivo results implicated a role for interleukin-6 in granuloma and MGC development. The in vitro granuloma model was used to investigate potential modulatory effects of this cytokine by analysing the cell numbers and the number of MGC per in vitro granuloma, the size of the MGC formed, the fusion index and the morphology of the in vitro granuloma. The results demonstrated significant modulatory effects of interleukin-6 on the cell number per in vitro granuloma and on the morphology of the cells involved. Conceivably, elevated interleukin-6 levels may modulate granuloma formation with respect to the number of cells involved and in influencing distinct cell populations involved in granuloma formation.
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    Central giant cell granuloma of the jawbones - new insights into molecular biology with clinical implications on treatment approaches
    (Murcia : F. Hernández, 2008) Vered, Marilena; Buchner, Amos; Dayan, Dan
    Central giant cell granulomas (CGCG) constitute about 10% of benign jawbone lesions. Approximately one-third of CGCG exhibit local aggressive behavior with bone destruction and a tendency to recur. Cure of patients with aggressive CGCG can be achieved by en bloc resection with clear margins at the possible cost of esthetic, functional and psychological problems, mainly in young patients. It is in these cases where pharmacologic agents are most needed as an alternative treatment approach. Until now, pharmacologic agents for CGCG have been used empirically and, in a small number of cases, with various degrees of success. The purpose of this review is to present the recent findings on the phenotypic profile of the constituent cells in CGCG at the molecular level and discuss the inter-relations among them; to analyze the osteolytic potential concealed in the lesional cells; to provide an evidence-based rationale for the use of pharmacologic agents, and, consequently, to suggest a revised approach for their use.
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    Endothelin-1 and endothelinconverting enzyme-1 in human granulomatous pathology of eyelid: an immunohistochemical and in situ hybridization study in chalazia
    (Murcia: F. Hernández, 2007) Massai, L.; Volpi, N.; Carbotti, P.; Fruschelli, M.; Mencarelli, M.; Pecorelli, A.; Muscettola, M.; Aglianò, M.; Alessandrini, C.; Grasso, G.
    Endothelin-1 (ET-1), a potent vasoconstrictor peptide, is involved in several functions of eye pathophysiology, such as regulation of intraocular tension and retinal reactive vasoconstriction. As ET-1 pro-inflammatory and fibrosing activity is emerging in different fields of pathology, we investigated the expression of ET-1 and endothelin-converting enzyme-1 (ECE-1) in chalazia, granulomatous lesions of the eyelid. ET-1 and ECE-1 were analyzed by immunohistochemistry (IHC) in twenty surgically removed chalazia, with regard to expression in eyelid structures and inflammatory infiltrate. Phenotype of ET-1 expressing inflammatory cells was established by double immunofluorescence. The cellular localization of prepro- ET-1 (pp-ET-1) mRNA and ECE-1 mRNA was studied by nonisotopic in situ hybridization (ISH). Neutrophils (PMNs), macrophages and Tlymphocytes were scattered in stroma, around alveoli and grouped in lipogranulomas. PMNs, macrophages, basal epithelium of meibomian adenomers and central ducts immunostained for ET-1. ECE-1 protein was found in meibomian adenomers, conjunctival epithelium, tarsal mucous glands and in inflammatory cells. Hybridization signals for pp-ET-1 mRNA and ECE-1 mRNA were recognized in healthy and degenerating meibomian ducts, adenomers, inflammatory cells, as well as in vessel walls. ECE-1 mRNA was also present in conjunctival epithelium and Henle’s crypts. Our findings suggest that the multifunctional peptide ET-1 may have a role in molecular genesis of tissue damage in chalazia. ET-1 cytokine activity is likely to support the migration of inflammatory cells and the setting of lipogranulomas; ET-1 stimulation might contribute to proliferation of fibroblasts and collagen synthesis. ET-1 upregulation on meibomian adenomers and ducts may further enhance granulomas formation by stimulating lipid release.