Granulocyte derived cationic peptide LL-37 prime hematopoietic progenitor cells through up-regulating glucose uptake and AMPK signaling (P2202)

Abstract

Abstract It has been reported that activated granulocytes derived cationic peptide LL-37 positively prime responsiveness of hematopoietic progenitor cells (HPCs) to CXCL12 gradient through an ambiguous pathway. The goal of this study was to elucidate the mechanism of enhanced migration of LL-37 primed HPCs to CXCL12 gradient. We performed in vitro migration assay and found out that LL-37 pretreatment enhanced migration of HPCs to CXCL12 only in the presence of D-glucose, but not in the absence of glucose or in the presence of glucose uptake inhibitor, 2-deoxy-D-glucose (2-DG). This signifies that LL-37 may affect intracellular energy production machinery. So we tested if the priming effect of LL-37 is related to mTOR signaling since mTOR is a central regulator of nutrient sensing and glycolysis promoting glucose uptake and ATP production to match energy demands for cell migration. As we expected, LL-37 induced glucose uptake in mTOR signaling dependent manner. Also, LL-37 induced the activation of nutrient sensing AMPK and its downstream substrates. In line with this, pretreatment of AMPK activator AICAR promoted migration of HSPCs as well. These findings demonstrate that the priming mechanism of LL-37 is closely associated with increasing ATP production and the optimization of glucose uptake and ATP production for HPCs prior to transplantation would be particularly important in HPCs transplantation where the number of cells available for transplantation is usually limited.