The influence of immune complex loading for the proinflammatory shift of the clearance of apoptotic neutrophils

• Antragstellerin: Professorin Dr. Sandra Franz
• Fachliche Zuordnung: Immunologie
• Förderung: Förderung von 2007 bis 2010
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 50275231

The cellular and molecular mechanisms leading to development of acute or chronic inflammation are not fully understood. Many human inflammatory diseases are associated with tissue deposition of immune complexes which may stimulate neutrophils that infiltrate inflammatory sites by engaging Fcγ receptors thereby exacerbating inflammation. We have recently reported the novel finding that IgG-containing immune complexes bind preferentially to apoptotic neutrophils via FcγRIIA. Furthermore, phagocytosis of immune complex-opsonised apoptotic neutrophils by human macrophages was substantially enhanced and stimulated macrophages to release small amounts of the pro-inflammatory cytokines TNFα and IL-6. The data implied that loading of apoptotic neutrophils with immune complexes alters their clearance pathway, and so has the potential to modulate the process of resolution of inflammation. In this proposal we will investigate the influence of immune complex binding to apoptotic neutrophils upon subsequent recognition and clearance by phagocytes. Furthermore, we will determine the effects of immune complex opsonisation on the presentation of apoptotic cell-associated antigens by human Dendritic cells. We predict that the immune complex-mediated pro-inflammatory clearance of apoptotic neutrophils will enhance cross-presentation of apoptotic cell-derived antigens, which may have implications for inflammation and autoimmunity.

• DFG-Verfahren: Forschungsstipendien
• Internationaler Bezug: Großbritannien
• Gastgeber: Professor Dr. Ian Dransfield