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

作者：Rembert Koczulla, Georges von Degenfeld, Christian Kupatt, Florian Krötz, Stefan Zahler, Torsten R. GLOE, Katja Issbrücker, Pia Unterberger, Mohamed Zaiou, Corinna Lebherz, Alexander Karl, Philip W J Raake, Achim Pfosser, Peter Boekstegers, Ulrich N. WELSCH, Pieter Sicco Hiemstra, Claus Franz Vogelmeier, Richard L. Gallo, Matthias A. Clauss, Robert Bals · 发表于：Journal of Clinical Investigation · 年份：2003 · DOI：10.1172/jci17545 · 被引用次数：855 · 研究领域：Antimicrobial Peptides and Activities、Biochemical and Structural Characterization、Peptidase Inhibition and Analysis

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.