Aim
Leukocyte-mediated inflammation is crucial in ST-segment elevation myocardial infarction (STEMI).  We recently observed that neutrophil extracellular traps (NETs) are increased at the culprit lesion site CLS, promoting the activation and differentiation of fibrocytes, cells with mesenchymal and leukocytic properties.  Fibrocyte migration is mediated by monocyte chemoattractant protein (MCP)-1 recognized via C-C chemokine receptor type 2 (CCR2).  We investigated the interplay between fibrocyte function, NETs and MCP-1 in STEMI.

Methods
CLS and femoral blood of STEMI patients (n=50) was drawn during percutaneous coronary intervention.  We characterized CCR2 expression of fibrocytes by flow cytometry.  MCP-1 and NET marker citrullinated histone H3 (citH3) were measured by ELISA.  Fibrocytes were treated in vitro with MCP-1.  Human coronary arterial endothelial cells (hCAECs) were stimulated with isolated NETs, and MCP-1 was measured by ELISA and qPCR.  The influence of MCP-1 on NET formation in vitro was assessed using isolated neutrophils. 

Results
Fibrocytes accumulated at the CLS in STEMI. Fibrocyte CCR2 expression was decreased compared with femoral control.  MCP-1 and citH3 were increased at the CLS.  CLS MCP-1 was correlated positively with fibrocyte accumulation, and negatively correlated with CCR2 expression.  In vitro, MCP-1 decreased fibrocyte CCR2.  NET stimulation of hCAECs induced MCP-1.  MCP-1 attenuated ionomycin-induced NETosis.

Conclusions
Fibrocyte accumulation at the CLS appears to be mediated by MCP-1.  NETs induce endothelial MCP-1, promoting a chemotactic gradient for fibrocyte migration.  The inhibitory effect of MCP-1 on NETosis might serve as a negative feedback loop, limiting inflammation.

02 - FIBROCYTES AND NEUTROPHIL EXTRACELLULAR TRAPS AT THE CULPRIT LESION SITE IN MYOCARDIAL INFARCTION: A ROLE FOR MONOCYTE CHEMOATTRACTANT PROTEIN 1