A13: Adenine Nucleotides in Immunity and Inflammation

This collaborative research consortium deals with unresolved issues regarding the signaling function of extracellular adenine nucleotides in inflammation, e.g. adenosine triphosphate or nicotinamide adenine dinucleotide), their modulation of the balance between pro- and anti-inflammatory processes by converting ecto-nucleotidases, and the timing and location of their release.

Our project, the project A13, is a collaboration of Prof. Dr. Tolosa’s lab in our Immunology department and our lab. In our project, we focus on the identification of the purine nucleotide metabolism machinery in the cellular compartments that are compromised in the course of stroke, namely the blood brain barrier (BBB) endothelial cells and microglia cells. We further target these components to manipulate the opening of the BBB and microglial inflammation.

Aim 1: To analyze the expression of purinergic ADO receptors and ectonucleotidases as well as their enzymatic activity by microglia and endothelial cells in vitro and in vivo (under conditions of stroke).

Aim 2: To determine the functional consequences of cell-specific deletion (microglia, endothelial cells) of ADO receptors and ecto-nucleotidases in stroke.

Aim 3: To identify ways to specifically modulate purinergic signaling at and behind the BBB.