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Göteborgs universitets publikationer

Basic characteristics of the neutrophil receptors that recognize formylated peptides, a danger-associated molecular pattern generated by bacteria and mitochondria.

Författare och institution:
Claes Dahlgren (Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning); Michael Gabl (Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning); André Holdfeldt (Institutionen för medicin); Malene Winther (Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning); Huamei Forsman (Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning)
Publicerad i:
Biochemical pharmacology, 114 s. 22-39
Artikel, forskningsöversikt
Sammanfattning (abstract):
Proper recruitment and activation of neutrophils to/at sites of infection/inflammation relies largely on the surface expression of chemoattractant receptors of which a formyl peptide receptor (FPR1) was the first to be cloned and characterized in more detail. This receptor displays high affinity for bacterial- or mitochondrial-derived peptides that contain a formylated methionine in the N-terminus. The neutrophil chemoattractant receptors belong to the group of 7-transmembrane domain receptors that signal through activation of heterotrimeric G proteins. These receptors have been shown to be important in host defense against microbial intruders and in regulating inflammatory reactions. The two FPRs (FPR1, FPR2) expressed in neutrophils share significant sequence homology and bind many structurally diverse activating (agonistic) and inhibiting (antagonistic) ligands, ranging from peptides to lipopeptides containing peptide sequences derived from intracellular regions of the FPRs. Recent structural and functional studies of the two neutrophil FPRs have generated important information for our understanding of general pharmacological principles, governing regulation of neutrophil function and inflammation and increased knowledge of more general G-protein coupled receptor features, such as ligand recognition, biased signaling, allosteric modulation, and a unique receptor cross-talk phenomenon. This article aims to summarize recent discoveries and pharmacological characterization of neutrophil FPRs and to discuss unmet challenges, including recognition by the receptors of diverse ligands and how biased signals mediate different biological effects.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Medicinska grundvetenskaper
Postens nummer:
Posten skapad:
2016-09-02 16:14

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