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The human antimicrobial peptide LL-37 induces endothelium-dependent vascular smooth muscle relaxation mediated via the lipoxin A4 receptor
Critical Care volume 11, Article number: P24 (2007)
Septic shock includes blood vessel dilatation and activation of innate immunity. The activation causes release of antimicrobial peptides such as LL-37. It has been shown that LL-37 can attract leukocytes via the lipoxin A4 receptor (ALX). ALX is also present in vascular endothelial cells. To explore possible ways of pharmacological intervention in septic shock, we investigated whether LL-37 can affect vascular tone.
Materials and methods
Human omental arteries and veins were obtained during abdominal surgery. The circular smooth muscle activity, in the wall of the vessel segments, was studied in organ baths. Gene expression was studied using reverse transcriptase PCR.
LL-37, at micromolar concentrations, induced a concentration-dependent and endothelium-dependent relaxation in vein segments 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), while it was less affected by the NOS inhibitor L-NAME and not at all by indomethacin. The ALX agonist, WKYMVm, did also induce a relaxation, and both the relaxations induced by LL-37 and WKYMVm were inhibited by the ALX antagonist WRWWWW. ALX was expressed in the endothelium.
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 the blood vessel dilatation during sepsis and treatment with ALX antagonists such as WRWWWW might be successful.
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Berkestedt, I., Nelson, A. & Bodelsson, M. The human antimicrobial peptide LL-37 induces endothelium-dependent vascular smooth muscle relaxation mediated via the lipoxin A4 receptor. Crit Care 11, P24 (2007). https://doi.org/10.1186/cc6003
- Nitric Oxide
- Septic Shock
- Potassium Chloride
- Organ Bath