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Endogenous antimicrobial peptide LL-37 induces human vasodilatation.

Berkestedt, Ingrid LU ; Nelson, A and Bodelsson, Mikael LU (2008) In British Journal of Anaesthesia 100. p.803-809
Abstract
BACKGROUND: /st> Septic shock includes blood vessel dilatation and activation of innate immunity, which in turn causes release of antimicrobial peptides such as LL-37. It has been shown that LL-37 can attract leucocytes via the lipoxin A(4) receptor (ALX, FPRL1). ALX is also present in vascular endothelial cells. To explore possible ways of pharmacological intervention in septic shock, we investigated if LL-37 can affect vascular tone. METHODS: /st> Human omental arteries and veins were obtained during abdominal surgery, and circular smooth muscle activity was studied in organ baths. Gene expression was studied using reverse transcriptase-polymerase chain reaction. RESULTS: /st> LL-37, at micromolar concentrations, induced a... (More)
BACKGROUND: /st> Septic shock includes blood vessel dilatation and activation of innate immunity, which in turn causes release of antimicrobial peptides such as LL-37. It has been shown that LL-37 can attract leucocytes via the lipoxin A(4) receptor (ALX, FPRL1). ALX is also present in vascular endothelial cells. To explore possible ways of pharmacological intervention in septic shock, we investigated if LL-37 can affect vascular tone. METHODS: /st> Human omental arteries and veins were obtained during abdominal surgery, and circular smooth muscle activity was studied in organ baths. Gene expression was studied using reverse transcriptase-polymerase chain reaction. RESULTS: /st> LL-37, at micromolar concentrations, induced a concentration- and endothelium-dependent relaxation in vein but not in artery segments precontracted by endothelin-1. The relaxation was profoundly reduced by potassium chloride (30 mM) to inhibit endothelium-derived hyperpolarizing factor (EDHF), whereas it was less affected by the NOS inhibitor, l-N(G)-nitroarginine methyl ester, and not at all by indomethacin. The ALX agonist, WKYMVm, also induced a relaxation and both the relaxations induced by LL-37 and WKYMVm were inhibited by the ALX antagonist, WRWWWW. ALX was expressed in the vein endothelium. CONCLUSIONS: /st> We demonstrate, for the first time, that the human antimicrobial peptide, LL-37, induces endothelium-dependent relaxation in human omental veins mediated via an effect on endothelial ALX. The relaxation involves the release of nitric oxide and EDHF but not prostanoids. LL-37 released from white blood cells could contribute to blood vessel dilatation during sepsis and treatment with ALX antagonists might be successful. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
British Journal of Anaesthesia
volume
100
pages
803 - 809
publisher
Macmillan
external identifiers
  • wos:000255987900013
  • pmid:18397922
  • scopus:44649135256
ISSN
1471-6771
DOI
10.1093/bja/aen074
language
English
LU publication?
yes
id
41933ab5-e583-40e5-82a3-b1df2fab5cf3 (old id 1147627)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18397922?dopt=Abstract
date added to LUP
2008-05-08 09:08:26
date last changed
2017-06-04 04:30:34
@article{41933ab5-e583-40e5-82a3-b1df2fab5cf3,
  abstract     = {BACKGROUND: /st> Septic shock includes blood vessel dilatation and activation of innate immunity, which in turn causes release of antimicrobial peptides such as LL-37. It has been shown that LL-37 can attract leucocytes via the lipoxin A(4) receptor (ALX, FPRL1). ALX is also present in vascular endothelial cells. To explore possible ways of pharmacological intervention in septic shock, we investigated if LL-37 can affect vascular tone. METHODS: /st> Human omental arteries and veins were obtained during abdominal surgery, and circular smooth muscle activity was studied in organ baths. Gene expression was studied using reverse transcriptase-polymerase chain reaction. RESULTS: /st> LL-37, at micromolar concentrations, induced a concentration- and endothelium-dependent relaxation in vein but not in artery segments precontracted by endothelin-1. The relaxation was profoundly reduced by potassium chloride (30 mM) to inhibit endothelium-derived hyperpolarizing factor (EDHF), whereas it was less affected by the NOS inhibitor, l-N(G)-nitroarginine methyl ester, and not at all by indomethacin. The ALX agonist, WKYMVm, also induced a relaxation and both the relaxations induced by LL-37 and WKYMVm were inhibited by the ALX antagonist, WRWWWW. ALX was expressed in the vein endothelium. CONCLUSIONS: /st> We demonstrate, for the first time, that the human antimicrobial peptide, LL-37, induces endothelium-dependent relaxation in human omental veins mediated via an effect on endothelial ALX. The relaxation involves the release of nitric oxide and EDHF but not prostanoids. LL-37 released from white blood cells could contribute to blood vessel dilatation during sepsis and treatment with ALX antagonists might be successful.},
  author       = {Berkestedt, Ingrid and Nelson, A and Bodelsson, Mikael},
  issn         = {1471-6771},
  language     = {eng},
  pages        = {803--809},
  publisher    = {Macmillan},
  series       = {British Journal of Anaesthesia},
  title        = {Endogenous antimicrobial peptide LL-37 induces human vasodilatation.},
  url          = {http://dx.doi.org/10.1093/bja/aen074},
  volume       = {100},
  year         = {2008},
}