Koczulla, Rembert; Degenfeld, Georges von; Kupatt, Christian; Krötz, Florian; Zahler, Stefan; Gloe, Torsten; Issbrücker, Katja; Unterberger, Pia; Zaiou, Mohamed; Lebherz, Corinna; Karl, Alexander; Raake, Philip; Pfosser, Achim; Boekstegers, Peter; Welsch, Ulrich; Hiemstra, Pieter S.; Vogelmeier, Claus; Gallo, Richard L.; Clauss, Matthias; Bals, Robert
An angiogenic role for the human peptide antibiotic LL-37/hCAP-18.
In: The Journal of Clinical Investigation, Vol. 111, Nr. 11: S. 1665-1672
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.