LL-37 Triggers Antimicrobial Activity in Human Platelets

Abstract

Platelets play a crucial role in hemostasis and the immune response, mainly by recognizing signals associated with vascular damage. However, it has recently been discovered that the antimicrobial peptide LL-37 activates platelets in functions related to thrombus formation and inflammation. Therefore, this work aims to evaluate the effect of LL-37 on the activation of antimicrobial functions of human platelets. Our results show that platelets treated with LL-37 increase the surface expression of receptors (Toll-like receptors (TLRs) 2 and -4, CD32, CD206, Dectin-1, CD35, LOX-1, CD41, CD62P, and αIIbβ3 integrins) for the recognition of microorganisms, and molecules related to antigen presentation to T lymphocytes (CD80, CD86, and HLA-ABC) secrete the antimicrobial molecules: bactericidal/permeability-increasing protein (BPI), azurocidin, human neutrophil peptide (HNP) -1, and myeloperoxidase. They also translate azurocidin, and have enhanced binding to Escherichia coli, Staphylococcus aureus, and Candida albicans. Furthermore, the supernatant of LL-37-treated platelets can inhibit E. coli growth, or platelets can employ their LL-37 to inhibit microbial growth. In conclusion, these findings demonstrate that LL-37 participates in the antimicrobial function of human platelets.

Role of antimicrobial peptide cathelicidin in thrombosis and thromboinflammation

“…Accordingly, plasma of mice with psoriasis (that show significantly increased levels of CRAMP) considerably activated wildtype platelets but failed to do so in Fpr2/3-deficient mice ( 87 ). In addition to classical platelet activation, both LL-37-stimulated human platelets but also platelet intrinsic cathelicidin showed considerable antibacterial activity in vitro characterized by increased binding and killing of bacteria ( 88 ). In summary, cathelicidin is a potent activator of platelets that contributes to thromboinflammation ( Figure 1 ).…”

“…Although cathelicidin is considered to have a short half-life, it is very likely that relevant amounts of neutrophil-derived cathelicidin are exposed to blood components and other cells at sites of thrombosis. Though, neutrophils are considered the main source of cathelicidin in thromboinflammation that have capacity of immediate release of high amounts with influence on acute processes ( 20 ), release by other cells such as monocytes/macrophages, endothelial, smooth muscle cells or even platelets ( 16 , 78 , 88 , 139 ) might contribute to ongoing inflammation with effects on development of chronic vascular diseases such as atherosclerosis ( 19 , 116 ) ( Table 1 ).…”