The antimicrobial peptide LL37 underpins thrombotic complications in inflammatory diseases

LL37 is a powerful antimicrobial peptide present in human epithelial cells of airways, intestine, skin and innate immune cells such as neutrophils and monocytes. It exhibits direct antimicrobial activities against a range of bacterial species, fungi and viruses. Furthermore, LL37 induces innate immunity and inflammatory responses to accelerate the clearance of microbial infection. Its roles in the regulation of leukocyte-mediated inflammatory responses at various pathophysiological settings have been studied. However, the effects of LL37 in the modulation of platelet function have not yet been established. Although platelets play indispensable roles in the regulation of haemostasis, their inappropriate activation under pathological conditions leads to thrombosis and blockage of blood supply to vital organs. Platelets are also involved in the regulation of inflammatory responses.

In this study, we propose to determine the effects of LL37 in the modulation of platelet reactivity, thrombosis and platelets-mediated inflammatory responses and elucidate the molecular mechanisms through which LL37 controls platelet function.

Determining the effects of LL37 in the control of platelet function under pathological conditions will provide a new paradigm in platelet biology and help to improve therapeutic strategies for cardiovascular and inflammatory diseases.