Characterization of the role of serotonin in the recruitment of neutrophils to sites of acute inflammation - potential for novel targeted therapy

• Applicant: Professor Dr. Daniel Dürschmied
• Subject Area: Cardiology, Angiology
• Term: from 2011 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 195340632

The vast majority of peripheral serotonin is stored in the granules of circulating blood platelets. Activated platelets release their granule contents at sites of inflammation and serotonin is believed to be a key inflammatory mediator. We recently found that serotonin plays a role in the recruitment of neutrophils, but the underlying mechanisms remain elusive. In preliminary knock-out experiments we saw a strong relationship between platelet serotonin and neutrophil extravasation in several models of acute inflammation. Here, we propose a series of experiments to evaluate whether neutrophil rolling, adhesion, or transmigration depends on serotonin and whether neutrophil chemotaxis or endothelial activation is regulated by serotonin. Mice lacking tryptophan hydroxylase I, the rate-limiting enzyme for the synthesis of peripheral serotonin, and wild-type mice treated with selective serotonin reuptake inhibitors will be used as models to study the function of serotonin delivery by platelets to inflamed vessels. Identification and inhibition of the involved receptors will allow proposing novel therapeutic strategies. Taken together, new insight into the mechanisms by which serotonin regulates acute inflammatory processes will be gained.

• DFG Programme: Research Grants