Analysis of the function of myeloid cells recruited to sites of tissue damage and the role of VEGF-A in these processes using conditional mutagenesis in mouse models

• Antragstellerin: Professorin Dr. Sabine Eming
• Fachliche Zuordnung: Dermatologie
• Förderung: Förderung von 2007 bis 2008
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 46567739

Macrophages and polymorphonuclear leukocytes of the myeloid lineage are key elements of the innate immune response following tissue injury. However, their role in cutaneous wound repair is not well understood. Our recent data indicate that VEGF-A, a crucial mediator of angiogenesis, vascular permeability and inflammation, is a key candidate to conduct myeloid-cell function during repair. Currently it is not known to which extent VEGF-A mediates these processes during the healing response. The aims of this proposal are i) to determine the role of the macrophage and neutrophil cell infiltrate for different repair mechanisms and ii) to identify the specific contribution of myeloid cell-derived VEGF-A to these processes. For this purpose, we will use a genetic mouse model in which we will inducibly ablate macrophages and neutrophils. This approach will enable us to identify cellular events during repair, which are dependent or independent of this infiltrate. Moreover, we will generate and wound mice with deletion of VEGF-A either in macrophages and neutrophils or with body wide inducible VEGF-A deficiency, to differentiate between VEGF-A repair signals released by the myeloid cell infiltrate or by additional cell types at the wound site. These studies provide a systematic approach to identify precisely the role of macrophages and neutrophils recruited to sites of tissue damage and will allow us to determine to which extent VEGF-A mediates the function of these cells. In the long term this project aims at the development of therapeutic targets for wound healing disorder.

• DFG-Verfahren: Sachbeihilfen