An angiogenic role for the human peptide antibiotic LL-37/hCAP-18
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
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
View: Text | PDF
Article Immunology

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

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

×

Figure 4

Options: View larger image (or click on image) Download as PowerPoint
Effects of LL-37 on endothelial cells in vitro. (a) In vitro proliferati...
Effects of LL-37 on endothelial cells in vitro. (a) In vitro proliferation assays. Different concentrations of LL-37 and controls were added to cultivated HUVECs. Numbers at the left of the graph indicate the numbers of cells per microliter of volume after 72 hours. VEGF was used as positive control. Additionally, we tested sLL-37, HNP-1, -2, and -3, hBD-3, and the propeptides hCAP-18. In vitro proliferation was not inhibited by human serum. Application of the FPRL1 agonist peptide WKYMVm (W peptide) results in increased growth of cell numbers. Addition of antiserum to FPRL1 blunted increased cellular proliferation induced by LL-37. *P < 0.05 as compared with the control group (n = 10/group). (b and c) Hamster aortic ring–sprouting assay. The addition of LL-37 to the culture medium resulted in increased sprouting from the aortic rings as compared with control groups that received bFGF or no peptide (b). *P < 0.05 in the LL-37 and bFGF groups as compared with the controls (n = 7/group) (c). aFPRL1, antiserum plus FPRL1.