Charakterisierung der MBL (mannose binding lectin)-abhängigen Aktivierungen des Komplementsystems bei der myokardialen Ischämie- und Reperfusion (MI/R), der Rolle von C1q bei MI/R sowie Charakterisierung der Mechanismen MBL-abhängiger myokardialer Schädigung nach MI/R

• Applicant: Privatdozent Dr. Marc Nicolai Busche
• Subject Area: General and Visceral Surgery ; Orthopaedics, Traumatology, Reconstructive Surgery
• Term: from 2005 to 2007
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5450978

Myocardial ischemia-reperfusion (MI/R) is a common clinical problem in the settings of vascular surgery and myocardial infarction. Complement activation plays an important role in local, and likely remote, tissue injury associated with MI/R. Recent evidence from our laboratory shows that blockade of mannose binding lectin (MBL) in vivo prevents deposition and activation of complement resulting in significantly reduced injury and attenduated inflammatory gene expression following MI/R 1-3. Using mice deficient in either C1q (inhibition of the classical pathway) or MBL (inhibition of the lectin pathway), or effector proteins downstream of both, I propose to identify the events leading to tissue destruction following experimental MI/R. In this proposal, I will investigate the role of MBL vs C1q (i.e.l lectin vs. classical pathway) following MI/R. I hypothesize that irreversible cardiac damage following MI/R is dependent on MBL and lectin complement pathway activation. The specific aims are as follows: 1) Characterize MBl-dependent complement activation in the initation of MI/R injury, and additionally evaluate the role of C1q in MI/R; 2) Determine the mechanism of MBL-dependent injury following MI/R.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Gregory Stahl