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dc.contributor.authorChapple, Cheryl Christine
dc.date.accessioned2009-04-22
dc.date.available2009-04-22
dc.date.issued2000-03-01
dc.identifier.urihttp://hdl.handle.net/2123/4467
dc.descriptionDoctor of Philosophyen
dc.description.abstractMacrophages play a critical role in many chronic inflammatory diseases. The pleiotrophic functional capacity of these cells includes phagocytosis and killing of opsonised microorganisms, antigen presentation to T cells, cytotoxicity and the secretion of potent angiogenic growth factors, of central importance in the maintenance or restoration of tissue homeostasis. Although the pathology of the chronic inflammatory disease, periodontitis, has been studied extensively there is a paucity of data relating to the role of macrophages. Recent studies of the untreated advanced periodontitis lesion have revealed extensive vascular pathology, including alteration in blood vessel morphology with thickening of the basement membrane, the accumulation of fragments of vascular basement membrane, persistence of foci of degenerate plasma cells and a restricted capacity to develop reparative granulation tissue. In relation to these pathological features, the distribution and functional status of macrophages assumes prime importance. Macrophage populations in untreated advanced periodontitis biopsies were compared with those in biopsies of clinically healthy, minimally inflamed, gingival tissue. The immunohistochemical investigation used high specificity monoclonal antibodies including a pan-macrophage marker and probes for acute inflammatory, resident histiocytic, and reparative macrophage phenotypes. Results indicated that advanced periodontits and minimally inflamed tissues displayed similar distribution patterns and numbers for the macrophage phenotypic markers. Regionally-specific differences in the populations occurred, however. Further studies investigated macrophage expression of the functional activation markers MHC class II for antigen presentation, and acid phosphatise (AP) and tartrate-resistant acid phosphatise (TRAP) for lysosomal enzyme activity. In the advanced periodontitis lesion there was little evidence of macrophage activation for the expression of HLA-DR and TRAP, although strong expression of HLA-DR was observed in association with blood vessels. Macrophages expressing AP showed a distinct regional distribution; however this was not associated with foci of degenerate plasma cells. These data support the hypothesis that macrophages do not express appropriate activation for key functions in the unrelated lesion of periodontitis. It is postulated that the apparent failure of recruitment and activation of macrophages may in part be both a cause and a consequence of the unusual pathological features of this disease. Although periodontisis is a chronic inflammatory disease of the highly vascularised supporting tissues of the teeth, little is known about the vascular changes in untreated advanced periodontitis. Observations of vascular features of the pathology were investigated and defined, forming the basis for a study of two angiogenic growth factors in periodontitis. In the connective tissue subjacent to the altered epithelium lining the periodontal pocket, there was a significant increase in the numerical density of vascular profiles, primarily accounted for by vessels ≥25μm in diameter. In addition, vascular basement membranes were thickened and there was regional accumulation of non-vascular basement membrane remnants. The co-localisation of type IV collagen and laminin and the discrete nature of these structures was confirmed, using 3-D reconstruction. The distribution of two major angiogenic growth factors, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), in untreated periodontitis was studied using immunohistochemistry. Basic fibroblast growth factor was not expressed by macrophages. Although bFGF was consistently associated with blood vessels, there was no regional variation in its distribution. In contrast, there was marked regional variation in the intensity of immunostaining for VEGF, with significantly reduced staining of the pocket epithelium. Few macrophages of the Ber-MAC3 phenotype expressed VEGF, as determined by dual immunofluorescence and confocal microscopy. It is considered that the changes in the vascularity of the periodontal connective tissues in untreated advanced periodontitis are, in part, a consequence of altered expression of angiogenic activity by the epithelium and limited expression of angiogenic growth factors by macrophages. Macrophage anergy and vascular disruption observed in the described studies indicate that tissue defence, maintenance and repair are compromised in the untreated lesion of advanced periodontitis.en
dc.publisherUniversity of Sydney.en
dc.publisherFaculty of Dentistryen
dc.rightsThe author retains copyright of this thesis.
dc.rights.urihttp://www.library.usyd.edu.au/copyright.html
dc.subjectMacrophagesen
dc.subjectPeriodontitisen
dc.titleThe characterisation of macrophage functions in untreated adult periodontitisen
dc.typePhD Doctorateen
dc.date.valid2000-01-01en


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