Activation of neutrophils - but not endothelial cells - is regulated by serotonin during myocardial reperfusion injury

M. Mauler, F. Glatzki, N. Herr, C. Schoenichen, T. Witsch, D. Stallmann, C. Bode, I. Ahrens, I. Hilgendorf, D. Duerschmied (Freiburg, Germany)

Arterial thrombosis
Date: 17.02.2017,
Time: 17:15 - 18:15

Objective: During reperfusion after myocardial infarction neutrophils migrate actively into the affected myocardium and a subset of these neutrophils form platelet neutrophil complexes (PNCs). Peripheral serotonin is synthesized by tryptophan hydroxylase isoform 1 (Tph1) and regulates neutrophil recruitment during acute inflammation

Methods: Myocardial infarction was induced in WT and Tph1-/- mice followed by 24 hours of reperfusion. Cardiac and blood neutrophils, endothelial cells were analyzed by histology and flow cytometry. Heart function and infarct size was determined by echocardiography and hisology.

Results: Infarct size was reduced by 33% in Tph1-/- mice and fractional shortening was significantly improved (25% vs. 12% in WT). Flow cytometry and histological preparation revealed dampened neutrophil migration into the affected myocardium in Tph1-/- mice compared to WT, whereas macrophage and monocyte populations were similar. We found a 50% decrease in neutrophil integrin alpha M expression on neutrophils of Tph1-/- mice. Interestingly, aortic ICAM expression was not affected by the lack of serotonin. This was also confirmed by in vitro stimulation of neutrophils and endothelial cells with serotonin.

Conclusion: Peripheral serotonin regulates CD11b on neutrophils, which is responsible for attachment and subsequent migration. Its counterpart, ICAM-1, on endothelial cells is not affected. This results in a milder inflammatory response during myocardial reperfusion injury in mice lacking peripheral serotonin.