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

J Clin Invest. 2003 Jun;111(11):1665-72. doi: 10.1172/JCI17545.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcysteine / pharmacology
  • Animals
  • Anti-Bacterial Agents / chemistry*
  • Antimicrobial Cationic Peptides / genetics
  • Antimicrobial Cationic Peptides / pharmacology*
  • Apoptosis
  • Blotting, Western
  • Calcium / metabolism
  • Cathelicidins
  • Cell Division
  • Cells, Cultured
  • Collagen / pharmacology
  • Cricetinae
  • Drug Combinations
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Indoles / pharmacology
  • Inflammation / metabolism
  • Ischemia
  • Laminin / pharmacology
  • Maleimides / pharmacology
  • Mesocricetus
  • Mice
  • NF-kappa B / metabolism
  • Neovascularization, Physiologic*
  • Peptides / chemistry
  • Prodrugs / pharmacology*
  • Proteoglycans / pharmacology
  • Rabbits
  • Receptors, Cell Surface / biosynthesis
  • Receptors, Formyl Peptide*
  • Receptors, Lipoxin*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Wound Healing

Substances

  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • Cathelicidins
  • Drug Combinations
  • Enzyme Inhibitors
  • FPR2 protein, human
  • Indoles
  • Laminin
  • Maleimides
  • NF-kappa B
  • Peptides
  • Prodrugs
  • Proteoglycans
  • Receptors, Cell Surface
  • Receptors, Formyl Peptide
  • Receptors, Lipoxin
  • matrigel
  • ropocamptide
  • Collagen
  • bisindolylmaleimide I
  • Calcium
  • Acetylcysteine