Rapid catecholamine trafficking regulates neutrophil functions and neutrophil-platelet interactions

Abstract

Neutrophils are key effector cells of the innate immune system that respond to small signaling molecules regulating immune responses. For a long time, similarities between neuronal and immune cells have been discussed. Here, we show that human neutrophils rapidly take up, package and use catecholamine neurotransmitters such as dopamine or epinephrine via the machinery known from neurons. Uptake and release of catecholamines as well as trafficking and packaging into MPO/VMAT2-positive primary vesicles is visualized with false fluorescent neurotransmitters. We also directly image the fast (> 10 s) and transient release of catecholamines from neutrophils with near infrared fluorescent nanosensors. Serotonin or activated platelets trigger calcium (Ca2+) signaling and consequently exocytosis of catecholamines. They reduce NET-formation but increase platelet aggregation. Thus, we establish similarities between neurons and neutrophils and identify a paracrine neutrophil-platelet feedback loop relevant for inflammatory and coagulatory conditions.