Complement Factor H in Intestinal Ischemia Reperfusion Injury : Mechanism Of Action

Complement factor H (CFH) is the major regulator of the alternative pathway of complement and mutations and genetic polymorphisms in the CFH gene predispose to severe human diseases. In this study a novel method of purifying CFH from pooled human plasma is demonstrated. Furthermore, the question is addressed of purified human CFH being successful option as therapeutic complement inhibitor in a preclinical model of human disease with implication of complement activation in its patho-mechanism. Intestinal ischemia reperfusion injury was induced in rats. Significant local complement deposition and local tissue injury on the ileal mucosa was determined providing a rationale to administer human CFH as therapeutic and subsequently test the hypothesis that intravenous application of human CFH would protect rats from clinical manifestations of intestinal IRI. The mechanism of action of therapeutic CFH in a rat model of a clinically relevant human disorder is lastly demonstrated and future prospects on CFH as therapeutic complement inhibitor are discussed in detail. This book focuses on scientists, post-docs and pre-doctoral students working in the field of translational complement biology.