Cathelicidin LL-37 peptide regulates endothelial cell stiffness and endothelial barrier permeability

Byfield FJ, Wen Q, Leszczynska K, Kulakowska A, Namiot Z, Janmey PA, Bucki R. Cathelicidin LL-37 peptide regulates endothelial cell stiffness and endothelial barrier permeability. Am J Physiol Cell Physiol 300: C105-C112, 2011. First published October 13, 2010; doi: 10.1152/ajpcell.00158.2010.-LL-37 peptide is a multifunctional host defense molecule essential for normal immune responses to infection or tissue injury. In this study we assess the impact of LL-37 on endothelial stiffness and barrier permeability. Fluorescence microscopy reveals membrane localization of LL-37 after its incubation with human umbilical vein endothelial cells (HUVECs). A concentration-dependent increase in stiffness was observed in HUVECs, bovine aortic endothelial cells (BAECs), human pulmonary microvascular endothelial cells, and mouse aorta upon LL-37 (0.5-5 mu M) addition. Stiffening of BAECs by LL-37 was blocked by P2X7 receptor antagonists and by the intracellular Ca2+ chelator BAPTAAM. Increased cellular stiffness correlated with a decrease in permeability of HUVEC cell monolayers after LL-37 addition compared with nontreated cells, which was similar to the effect observed upon treatment with sphingosine 1-phosphate, and both treatments increased F-actin content in the cortical region of the cells. These results suggest that the antiinflammatory effect of LL-37 at the site of infection or injury involves an LL-37-mediated increase in cell stiffening that prevents increased pericellular permeability. Such a mechanism may help to maintain tissue fluid homeostasis.