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

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1665-1672
Number of pages8
JournalJournal of Clinical Investigation
Volume111
Issue number11
StatePublished - Jun 2003
Externally publishedYes

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Anti-Bacterial Agents
Endothelial Cells
Peptides
Wounds and Injuries
Formyl Peptide Receptor
Inflammation
Chorioallantoic Membrane
Innate Immunity
Immune System
Leukocytes
Ischemia
Extremities
Epithelial Cells
Rabbits
Skin
CAP18 lipopolysaccharide-binding protein
cathelicidin antimicrobial peptide
antimicrobial peptide LL-37

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Koczulla, R., Von Degenfeld, G., Kupatt, C., Krötz, F., Zahler, S., Gloe, T., ... Bals, R. (2003). An angiogenic role for the human peptide antibiotic LL-37/hCAP-18. Journal of Clinical Investigation, 111(11), 1665-1672.

An angiogenic role for the human peptide antibiotic LL-37/hCAP-18. / Koczulla, Rembert; Von Degenfeld, Georges; 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.

In: Journal of Clinical Investigation, Vol. 111, No. 11, 06.2003, p. 1665-1672.

Research output: Contribution to journalArticle

Koczulla, R, Von Degenfeld, G, Kupatt, C, Krötz, F, Zahler, S, Gloe, T, Issbrücker, K, Unterberger, P, Zaiou, M, Lebherz, C, Karl, A, Raake, P, Pfosser, A, Boekstegers, P, Welsch, U, Hiemstra, PS, Vogelmeier, C, Gallo, RL, Clauss, M & Bals, R 2003, 'An angiogenic role for the human peptide antibiotic LL-37/hCAP-18', Journal of Clinical Investigation, vol. 111, no. 11, pp. 1665-1672.
Koczulla R, Von Degenfeld G, Kupatt C, Krötz F, Zahler S, Gloe T et al. An angiogenic role for the human peptide antibiotic LL-37/hCAP-18. Journal of Clinical Investigation. 2003 Jun;111(11):1665-1672.
Koczulla, Rembert ; Von Degenfeld, Georges ; 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: Journal of Clinical Investigation. 2003 ; Vol. 111, No. 11. pp. 1665-1672.
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AU - Kupatt, Christian

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AU - Zahler, Stefan

AU - Gloe, Torsten

AU - Issbrücker, Katja

AU - Unterberger, Pia

AU - Zaiou, Mohamed

AU - Lebherz, Corinna

AU - Karl, Alexander

AU - Raake, Philip

AU - Pfosser, Achim

AU - Boekstegers, Peter

AU - Welsch, Ulrich

AU - Hiemstra, Pieter S.

AU - Vogelmeier, Claus

AU - Gallo, Richard L.

AU - Clauss, Matthias

AU - Bals, Robert

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N2 - 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.

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