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Thesis Bas Zwart
On 30 March 2010 Bas Zwart will defend his thesis 'Processing of apoptotic cells in health and systemic autoimmune disease' at the University of Amsterdam. Promotor: Prof. dr. L.A. Aarden The research for this thesis was performed at the Department of Immunopathology of Sanquin Research, and the Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, The Netherlands. Summary In this thesis the binding of plasma proteins to cells in an early and late phase of programmed cell death, apoptosis, is described. Binding of plasma proteins to early apoptotic cells is trivial, whereas plasma protein binding in late apoptotic cells is strongly increased. Binding of plasma proteins to early apoptotic cells in healthy donor plasma or in plasma of patients with systemic lupus erythematosus (SLE) is comparable. SLE is characterised by the production of antibodies specific for various cellular constituents, especially antinuclear antigens (ANA). Late apoptotic cells in SLE plasma display increased binding of IgG and C1q to late apoptotic cells, compared to healthy donor plasma. Interestingly, late apoptotic cells release remnants of the nucleus, so called nucleosomes, in healthy donor plasma. This nucleosome releasing factor (NRF) activity is absent in a subset of SLE plasmas. NRF is inhibited in the presence of ANA.in SLE plasma. NRF activity is exerted by factor VII activating protein (FSAP). Contents Chapter 1 Introduction Chapter 2 Chromatin-independent binding of serum amyloid P component to apoptotic cells. J Immunol 2001; 167(2):647-54. Chapter 3 Binding of the phospholipid-binding plasma proteins β2-glycoprotein-I, serum amyloid P component and C-reactive protein to apoptotic cells is not defective in SLE. Chapter 4 Complement activation by apoptotic cells occurs predominantly by IgM and is limited to late apoptotic (secondary necrotic) cells. Eur J Immunol 2004; 34(9):2609-19. Chapter 5 Binding of IgG and C1q to late apoptotic cells is increased in SLE plasma; a role for IgG antinuclear antibody (ANA) as activator of complement? Chapter 6 A plasma nucleosome releasing factor (NRF) with serine protease activity is instrumental in removal of nucleosomes from secondary necrotic cells. FEBS Lett 2007; 581(28):5382-8 Chapter 7 Nucleosome releasing factor (NRF) activity in plasma from SLE patients. Chapter 8 Nucleosome Releasing Factor: a new role for factor VII-activating protease (FSAP) FASEB J 2008; 22(12):4077-84 Chapter 9 General discussion Top | Order this thesis Click here for earlier published theses Contents |