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An angiogenic role for the human peptide antibiotic LL-37/hCAP-18
Rembert Koczulla, … , Matthias Clauss, Robert Bals
Rembert Koczulla, … , Matthias Clauss, Robert Bals
Published June 1, 2003
Citation Information: J Clin Invest. 2003;111(11):1665-1672. https://doi.org/10.1172/JCI17545.
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Article Immunology

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

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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.

Authors

Rembert Koczulla, Georges von Degenfeld, Christian Kupatt, Florian Krötz, Stefan Zahler, Torsten Gloe, Katja Issbrücker, Pia Unterberger, Mohamed Zaiou, Corinna Lebherz, Alexander Karl, Philip Raake, Achim Pfosser, Peter Boekstegers, Ulrich Welsch, Pieter S. Hiemstra, Claus Vogelmeier, Richard L. Gallo, Matthias Clauss, Robert Bals

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Figure 1

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LL-37 induces physiologic angiogenesis in the CAM assay. (a) LL-37 (5 μg...
LL-37 induces physiologic angiogenesis in the CAM assay. (a) LL-37 (5 μg/pellet) induces the formation of wheel spoke–like vessel formation in comparison with the scrambled control peptide sLL-37 or the solvent. bFGF was used as positive control. Bars: 1 mm. (b) Cross sections of CAMs. LL-37 increases the number of erythrocyte-filled vessels (Masson-Goldner stain of erythrocyte-filled vessels). Bars: 250 μm or 62 μm in the ×10 and ×40 micrographs, respectively. (c) The numbers of erythrocyte-filled vessels were counted in hot spots. *P < 0.05 as compared with the solvent group (n = 6/group; three sections per CAM).

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ISSN: 0021-9738 (print), 1558-8238 (online)

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