Prof. Dr. S.s. Zeerleder
Internal Medicine: Clinical Haematology, Landsteiner Laboratory
S.S. Zeerleder is one of the AMC Principal Investigators
Upon cell damage and cell death molecular structures, so-called damage-associated molecular pattern (DAMPs) are released into the circulation and induce a systemic inflammatory response by ligation of pattern recognition receptors (PRR). DAMPs released from nucleated cells include- among others- extra-cellular (cell-free) DNA, DNA-binding proteins (e.g. Histones, HMGB-1) and heme. DAMPs released from erythrocytes comprise hemoglobin, iron and heme, respectively. Extracellular DNA, e.g nucleosomes, and HMGB1 have been demonstrated to induce an inflammatory response via Toll-like receptor (TLR) 9 and histones via TLR2 and TLR4, respectively. Heme is cytotoxic through the formation of highly active reactive oxygen species (ROS), an effect that is - in part - dependent on TLR4 and induction of the NFkappaB pathway.