Doctor of Philosophy / This thesis describes work done at the Institute of Dental Research in Sydney between February of 1986 and January 1990. The broad subject of the work is the role of vascular endothelial cells (ECs) in chronic inflammation. Periodontitis has been used as an example of chronic inflammatory disease, and provides the focus for this study of endothelial biology. In Chapter 1, aspects of the endothelial literature which provide relevant background information for work described in later chapters are reviewed. In Chapter 2, literature relating to aetiology and pathogenesis of chronic inflammatory periodontal disease is discussed. To maintain relevance of literature reviews to experimental work, each subsequent chapter contains a small literature review of material relating to the subject of the specific chapter. Early laboratory work is described in Chapter 3, and consisted of a morphological survey of the vascular changes occurring in gingival tissues with development of chronic periodontitis. Expansion of the vasculature and appearance of phenotypically specialised high endothelial cells (HECs), were associated with progression of the disease. Vessels with HECs and had a similar appearance to those known to be responsible for lymphocyte recirculation described in lymphoid tissues and chronic inflammatory sites. In the course of performing this survey, a perivascular hyaline material was noted surrounding capillaries close to the bacterial plaque irritant. The incidence, distribution, extent, ultrastructre and immuo-histochemistry of this material was more closely investigated, and the possible pathogenesis and significance of the material discussed in Chapter 4. In Chapter 5, the ultrastructural, histochemical and functional properties of gingival HECs are described, and compared with the well characterised HECs of rat lymph nodes. It was found that periodontal vessels were very similar to those in rat lymph nodes, with the exception however, that the gingival vessels appeared to exchange polymorphonuclear leukocytes almost exclusively, while vessels with HECs in lymph nodes and other locations are known as sites of lymphocyte recirculation. This observation indicated that the function of HECs requires further investigation, with particular regard to the synthetic activity of the cells. HECs were consistently alkaline phosphatise (AP) negative. The negative association between leukocyte emigration and AP activity (APA), as well as evidence in the literature illustrating both the wide substrate specificity of this enzyme and the importance of phosphorylation in the control of protein activation, suggested that AP could play a role in regulating leukocyte emigration. A pre-requisite for the investigation of this possibility, is the identification of a rich source of the identical iso-enzyme of AP to what is present in ECs. In Chapter 6, the sensitivity of endothelial AP to a panel of inhibitors is compared with that of a number of tissues for which isoenzyme has been identified. Endothelial AP was identified as the liver/bone/kidney isoenzyme. This allows the use of kidney tissue as a relevant source of AP for use in further study of the role of this enzyme in EC biology. It was clear that in order to study both the synthetic activity of HECs, as well as the role of AP in the control of leukocyte emigration, a method for obtaining high density primary cultures of HECs had to be established. Chapter 7 describes work done towards the development of such a culture system. The availability in the latter phase of the work of suitable probe for the technique of the in-situ hybridization allowed the possibility of testing the hypothesis that HECs are important cytokine producers. It was felt that this would provide some basis for the further study of those cells in-virtro. This work is described in the appendix. The general discussion in Chapter 8, summarises the work, and develops potential areas of study arising from the finding of this thesis.
| Identifer | oai:union.ndltd.org:ADTP/283637 |
| Date | January 1991 |
| Creators | Zoellner, Hans |
| Publisher | University of Sydney., Faculty of Dentistry |
| Source Sets | Australiasian Digital Theses Program |
| Detected Language | English |
| Rights | The author retains copyright of this thesis., http://www.library.usyd.edu.au/copyright.html |
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