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
-
Collagen
-
bisindolylmaleimide I
-
Calcium
-
Acetylcysteine