This thesis focuses on describing novel methodology for studying the complement system in experimental rodent models, on fundamental aspects of mouse complement, and the activation and... Show moreThis thesis focuses on describing novel methodology for studying the complement system in experimental rodent models, on fundamental aspects of mouse complement, and the activation and contribution of complement system in experimental renal ischemia/reperfusion (I/RI) and renal autoimmune disease animal models. Our findings show that transient and acute complement activation is observed following renal I/RI and that the developed and validated methodology for analysis of systemic complement can be a valuable addition to complement analysis in preclinical studies. Our novel findings included the characterisation of C5a receptor C5L2 and its contribution to renal I/RI. Our results revealed injurous contribution to the pathology of renal I/RI, in similar degree as with C5aR. Using anti-GBM renal autoimmune disease as an experimental model, we showed for the first time in vivo that properdin, the only positive regulator of complement, may direct complement activation independent of classical ligands such as C3. Other findings included the characterisation of drastic gender difference in mouse complement, where female mice have near-deficient terminal pathway serum activity, and the impact of therapeutic dietary restriction on serum complement, which was shown to downregulate the hepatic expression of the terminal pathway components in serum. Show less
Poppelaars, F.; Werkhoven, M. van; Kotimaa, J.; Veldhuis, Z.; Ausema, A.; Broeren, S.; ... ; Seelen, M. 2016
