An angiogenic role for the human peptide antibiotic LL-37/hCAP-18

TLDR

Antimicrobial peptides are key innate immune effectors that defend against pathogens and modulate inflammation, and the human cathelicidin LL‑37/hCAP‑18 is produced by leukocytes and epithelial cells and released into wound and airway fluids. The study aims to determine whether LL‑37 induces angiogenesis through the formyl peptide receptor–like 1 expressed on endothelial cells. LL‑37 directly activates endothelial cells, stimulating proliferation and vessel‑like structure formation in vitro. LL‑37 promotes neovascularization in the chorioallantoic membrane assay and a rabbit hind‑limb ischemia model, and loss of its murine homologue CRAMP impairs wound‑repair vascularization, demonstrating its essential role in angiogenesis and arteriogenesis.

Abstract

Antimicrobial peptides are effector molecules of the innate immune system and contribute to host defense and regulation of inflammation. The human cathelicidin antimicrobial peptide LL-37/hCAP-18 is expressed in leukocytes and epithelial cells and secreted into wound and airway surface fluid. Here we show that LL-37 induces angiogenesis mediated by formyl peptide receptor–like 1 expressed on endothelial cells. Application of LL-37 resulted in neovascularization in the chorioallantoic membrane assay and in a rabbit model of hind-limb ischemia. The peptide directly activates endothelial cells, resulting in increased proliferation and formation of vessel-like structures in cultivated endothelial cells. Decreased vascularization during wound repair in mice deficient for CRAMP, the murine homologue of LL-37/hCAP-18, shows that cathelicidin-mediated angiogenesis is important for cutaneous wound neovascularization in vivo. Taken together, these findings demonstrate that LL-37/hCAP-18 is a multifunctional antimicrobial peptide with a central role in innate immunity by linking host defense and inflammation with angiogenesis and arteriogenesis.