Mast cell-related mechanisms in oral lichen planus

Zhao, Zhen Zhen. (2002). Mast cell-related mechanisms in oral lichen planus PhD Thesis, School of Dentistry, The University of Queensland.

       
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Author Zhao, Zhen Zhen.
Thesis Title Mast cell-related mechanisms in oral lichen planus
School, Centre or Institute School of Dentistry
Institution The University of Queensland
Publication date 2002
Thesis type PhD Thesis
Supervisor Associate Professor Neil W. Savage
Professor Laurence J. Walsh
Total pages 103
Language eng
Subjects 320804 Dental Therapy
Formatted abstract
Oral lichen planus (OLP) is a chronic inflammatory disease in which cell-mediated immunity is believed to play an essential role. Current knowledge suggests that oral mucosal T lymphocytes and mast cells may be important in the induction phase of the pathogenesis of OLP, both promoting the development of the lesion and exerting immunoregulatory effects on the established lesion via release of C5^okines and other mediators. The characteristic and extensive infiltrate of T cells and mast cells in the OLP lesion has been characterized immunohistologically by a number of studies and compared with normal mucosa. Such observations, together with the wide spectrum of mediators produced and secreted by mast cells, have led to the concept of a functional relationship between mast cells and T cells in OLP.

Mast cells are known primarily for their role in inflammatory processes. They participate in the regulation of immune responses by releasing both preformed and newly synthesized mediators following appropriate stimulation. A fluorometric microassay was developed to determine in vitro histamine release from human gingival mast cells. The data obtained using this assay support the view that non-immunologic stimuli rather than immunologic stimuli, initiate mast cell degranulation in the oral cavity.

It has been proposed that mast cells degranulate in the early phases of OLP before the influx of effector lymphocytes. Mast cell-derived TNF-[alpha] may contribute to chemokine regulation of T cells in OLP. It was shown that OLP lesional T cells produce and secrete RANTES (regulated on activation, normal T-cell expressed, and secreted), which is up-regulated by TNF-[alpha]. Conversely, u T cell-derived RANTES was demonstrated to trigger mast cell degranulation and to promote mast cell migration. Moreover, OLP lesional T cell supernatants were found to regulate the proliferation in vitro of a human mast cell line.

Chemokines mediate their biological effects by binding to cell surface receptors. Several RANTES receptors have been identified including CCRl, CCR3, CCR4, CCR5, CCR9 and CCRIO. The regulation of cell chemokine receptor expression remains uncertain. It was found that OLP lesional T cell supematants up-regulated CCRl mRNA expression, and TNF-a upregulated CCRl, CCR4 and CCR5 mRNA expression in HMC-1 in vitro. Moreover, RANTES and RANTES receptor (CCRl) were shown to be expressed by T cells and mast cells in OLP in vivo.

In summary, there is strong support for a role for both T cells and mast cells in the immunopathogenesis of oral lichen planus (OLP). In this study, the interactions between mast cells and T cells in OLP were explored, which revealed both the complexity and subtlety of immune regulation in this condition. From these data, an hypothesis for the immunopathogenesis of OLP was then developed and presented, which stresses the bilateral nature of those mast cell-T cell interactions which dictate cellular activation, cell migration, and cell survival.

Keyword Dental therapeutics.
Additional Notes

Variant title: Mast cell mechanisms in lichen planus

Document type: Thesis
Collection: UQ Theses (RHD) - UQ staff and students only
 
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Created: Thu, 09 Dec 2010, 16:54:46 EST by Ms Sarah Mcdowell on behalf of Social Sciences and Humanities Library Service