No description available.

Doctor of Philosophy / Macrophages 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.

"December 2004" / Bibliography: leaves 159-180. / xii, 205 leaves : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / "The presence of macrophages within ovarian tissue has been acknowledged for many years. There is substantial evidence showing typical macrophage products such as interlukin-1-beta (IL-1B) and tumour necrosis factor alpha (TNFa), can significantly influence ovarian functions. To date the specific role these cells play in ovarian function has only been postulated. It was the aim of the work presented in this thesis to determine firstly, if these cells are critical to normal ovarian function, secondly to develop a method for isolating these cells from other ovarian cell types and thirdly, to examine the cytokine profile of these cells with the intention of determining which important inflammatory cytokines these cells are producing."--p. v. / Thesis (Ph.D.)--University of Adelaide, Faculty of Health Sciences, Dept. of Obstetrics and Gynaecology, 2005

Macrophage manipulation as immunomodulatory intervention in glaucoma, a leading cause to blindness characterized by retinal ganglion cell (RGC) loss, has been proposed as a promising strategy to protect RGCs from dying. Three types of macrophage in damaged retinas, microglia-derived macrophage, monocyte-derived macrophage and perivascular macrophage, together consist a highly heterogeneous population with both beneficial and detrimental functions partly resulted from their distinct origins. NG2 (Nerve/glial antigen 2) positive macrophage, a subtype of macrophage, has been considered to fulfill specific functions with neuroprotective and neurogenic potentials. Whether NG2+ macrophage can be a possible target for treatment in glaucoma is unknown. Basic information of this subtype of macrophage in ischemic retinas of a mouse glaucomatous model called acute ocular hypertension (AOH) model was obtained in this study to answer three questions. First, do NG2+ macrophage exist in mouse retina, if so, what do they like? In normal mouse retinas, NG2+ macrophage did not exist. After AOH, NG2 could be induced on macrophage. And they are unevenly distributed in the whole retina while reside in the ganglion cell layer, inner plexiform layer or inner nuclear layer. Moreover, NG2+ macrophage all contained two nuclei with typical amoeboid-like morphologies of macrophage in activation state except the rounded type. Secondly, are they associated with the surrounding cells, if so, how? Close association of RGCs and Müller cells with NG2+ macrophage was found due to their co-localization. To know how they functioned, potential roles regarding its proliferating and phagocytic abilities were revealed by its co-localization with proliferating and phagocytic markers. However, unlike NG2+ macrophage in ischemic brain, NG2+ macrophage in ischemic retina did not express neurotrophic factors while some of them were found to express interlukin-10, an anti-inflammatory cytokine. Possible neurogenic potential was also observed by its co-localization with Nestin, a neural stem cell marker. Thirdly, where do they come from? To know their origins, bone marrow chimeras combined with specific markers were used to distinguish microglia-derived macrophage, monocyte-derived macrophage and perivascular macrophage. And it was found that majority of NG2+ macrophage was originated from resident microglia, rather than monocyte-derived macrophage or perivascular macrophage. Taken together, the present study showed the basic profile of a subtype of macrophage in a mouse model of glaucoma, more accurately, NG2+ macrophage in AOH mouse retinas. NG2 expression was induced mostly in resident microglia in AOH retina as a proliferating population with phagocytic, anti-inflammatory functions, and possible neurogenic potentials. Therefore, NG2+ macrophage may be a potential candidate target for treatment of glaucoma. / published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy

No description available.

No description available.

Doctor of Philosophy / Macrophages 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.

Thesis (Ph.D.) -- University of Adelaide, Dept. of Human Physiology and Pharmacology, 1971.

Thesis (Ph. D.)--University of Adelaide, Faculty of Health Sciences, Dept. of Obstetrics and Gynaecology, 2005. / "December 2004." Includes bibliographical references (leaves 159-180).

Thesis (Ph. D.)--University of Sydney, 2000. / Title from title screen (viewed Apr. 27, 2009) Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the Department of Oral Biology, Faculty of Dentistry. Includes bibliography. Also available in print form.