An annexin 1 N-terminal peptide activates leukocytes by triggering different members of the formyl peptide receptor family.
The human N-formyl peptide receptor (FPR) is a key modulator of chemotaxis directing granulocytes toward sites of bacterial infections. FPR is the founding member of a subfamily of G protein-coupled receptors thought to function in inflammatory processes. The other two members, FPR-like (FPRL)1 and FPRL2, have a greatly reduced affinity for bacterial peptides or do not bind them at all, with FPRL2 being considered an orphan receptor so far. In this study we show that a peptide derived from the N-terminal domain of the anti-inflammatory protein annexin 1 (lipocortin 1) can activate all three FPR family members at similar concentrations. The annexin 1 peptide initiates chemotactic responses in human monocytes that express all three FPR family members and also desensitizes the cells toward subsequent stimulation with bacterial peptide agonists. Experiments using HEK 293 cells stably expressing a single FPR family member reveal that all three receptors can be activated and desensitized by the N-terminal annexin 1 peptide. These observations identify the annexin 1 peptide as the first endogenous ligand of FPRL2 and indicate that annexin 1 participates in regulating leukocyte emigration into inflamed tissue by activating and desensitizing different receptors of the FPR family.
Ernst
Stefanie
S
Institute for Medical Biochemistry, Center for Molecular Biology of Inflammation, von Esmarch-Strasse 56, D-48149 Münster, Germany.
Lange
Carsten
C
Wilbers
Andreas
A
Goebeler
Verena
V
Gerke
Volker
V
Rescher
Ursula
U
D017305:Annexin A1 / Q000494:pharmacology*; D020013:Calcium Signaling; D002460:Cell Line; D002634:Chemotaxis, Leukocyte; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology*; D008024:Ligands; D010455:Peptides; D044042:Receptors, Formyl Peptide / Q000819:agonists / Q000187:drug effects* / Q000502:physiology*; D044067:Receptors, Lipoxin / Q000819:agonists; D020298:U937 Cells
D017305:Annexin A1; C469986:FPR1 protein, human; C105101:FPR2 protein, human; C469985:FPR3 protein, human; D008024:Ligands; D010455:Peptides; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; C489643:annexin A1 peptide (1-25)