The role of cellular adhesion molecules in renal transplantation.
2015-11-19T08:50:32Z (GMT) by
This thesis investigates the role of endothelial cell adhesion molecules in the process of renal transplantation, both by an in-vitro cell culture system using human umbilical vein endothelial cells (HUVECS) and in-vivo by immunohistological analysis of biopsies taken from renal allografts. In Chapter 1 the clinical problems associated with renal failure and renal transplantation are reviewed as well an historical perspective of renal transplantation and an overview of the immunological problems which may occur in a renal allograft. The cellular and molecular mechanisms involved in the inflammatory process are reviewed in Chapter 2, with particular reference to the role of endothelial cell adhesion molecules and inflammatory cytokines. In-vivo studies of cell adhesion molecules are also reviewed. In Chapter 3 the materials and methods employed are recorded. In Chapter 4 studies of endothelial cell adhesion molecule expression as measured by flow cytometry of HUVECS, with or without cytokine stimulation, are presented, showing that different adhesion molecules are expressed under different conditions and at different times. Chapter 5 investigates two assays for the measurement of polymorphonuclear leucocyte, (PMN), adhesion to HUVECS. A radioactive chromium release assay is used in preference to one employing Rose Bengal dye. The optimum assay conditions are investigated and used to produce a normal range for adhesion of PMN's from normal subjects. Adhesion of PMN's from renal transplant and haemodialysis patients is compared to that of normals in Chapter 6, showing that PMN's from transplant and haemodialysis patients demonstrate increased adherence to HUVECS. Chapter 7 investigates the expression and distribution of endothelial cell adhesion molecules on biopsies taken from renal allografts both pre and post transplantation. The distribution of adhesion molecules within the kidney is related to clinical events and shows that their expression alters in different pathological states. Chapter 8 is a general discussion of the results of the experimental work.