Interactions between mast cells and neutrophils in murine models of acute inflammation

• Applicant: Professor Dr. Michael Stassen
• Subject Area: Dermatology
• Term: from 2012 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 222284137

Neutrophils are critical for the innate host defence against invading pathogenic microorganisms. From diverse murine models for acute inflammation it can be concluded that the rapid recruitment of neutrophils to the inflamed tissues can be initiated by mast cells. Upon stimulation, mast cells are able to very rapidly release both preformed and de novo generated mediators acting on endothelial cells lining the blood vessels. This activation of endothelial cells is a prerequisite for docking and extravasation of neutrophils. In this context, our pilot experiments in the murine system show that mast cells can also directly promote the activation of neutrophils. Notably, neutrophil phagocytosis is strongly increased in the presence of activated mast cells. Interestingly, our unpublished data also suggest that activated neutrophils in turn are able to deliver co-activatory signals to mast cells with regard to degranulation and production of mast cell-derived cytokines. This interplay between mast cells and neutrophils is so far widely unrecognized and will be the main objective of this project. Investigations will be performed in vitro using pure populations of both cell types in order to identify the underlying mechanisms of this cross-talk. These experiments will be substantiated by animal experiments employing several strains of mast cell-deficient mice in models for acute inflammation with a focus on clinically relevant pulmonary aspergillosis.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1394: Mast Cells - Promoters of Health and Modulators of Disease
• Participating Person: Professor Dr. Markus P. Radsak