p33 project

p33 (also known as gC1q receptor) is a negatively charged surface protein found on many cell types including endothelial cells, neutrophils, lymphocytes, and platelets. Originally, p33 was identified as a receptor for complement factor C1q, but over the years also other ligands including high molecular weight kininogen and coagulation factor XII have been described. Interestingly p33 is also found intracellularly for instance in mitochondria or nucleus.Recent studies have shown that p33, also known as gC1q receptor (gC1qR), prevents cellular damage caused by bacteriolytic substances for instance antimicrobial peptides and extracellular histones. Notably, many bacteriolytic agents can in addition act as danger associated molecular pattern molecules (DAMPs) and exert pro- and anti-inflammatory as well as chemotactic properties. However, not much is known about how the activity of these DAMPs is regulated. Thus, this project aims to decipher the role of p33 in modulating the inflammatory response evoked by DAMPs. To this end, it is planned to focus on extracellular histones and LL-37, as both are found in close proximity to the site of infection and tissue necrosis. We will employ in vitro and ex vivo models such as cell migration assays, measurement of inflammatory mediators, and microscopic analysis and it is also intended to develop animal models to study the role of p33 in vivo.