Disruption of Glycosaminoglycan - Chemokine interaction in vivo reduces neutrophil activation and liver injury

Glycosaminoglycans (GAGs) are molecules involved in chemokine retention inside the vasculature. Chemokines act by binding to GAGs in endothelial cells and forming a gradient that drives leukocyte activation and inflammation. This important step was poorly explored in vivo, especially in organs with atypical vasculature such the liver. Thus, we aimed to evaluate hepatic GAG-chemokine interactions in vivo and the consequences of its disruption in neutrophil activation during hepatic inflammation. Using a labeled GAG-binding peptide we observed the liver has abundant GAG expression, which increases during a toxic injury. Also, we observed neutrophils accumulate in the injured liver, and increase movement parameters (track length, velocity, displacement, time span), cell area and polarization. Interestingly, treatment with a GAG-blocking peptide was able to reduce liver injury, neutrophil activation and inflammation. Concluding, our data indicates chemokine retention by GAGs in the liver is necessary for proper neutrophil activation and hepatic inflammation.status: accepte