Chemotaxis of dendritic cells (DCs) and monocytes is a key step in the initiation of an adequate immune response. Formyl peptide receptor (FPR) and FPR-like receptor (FPRL)1, two G protein–coupled receptors belonging to the FPR family, play an essential role in host defense mechanisms against bacterial infection and in the regulation of inflammatory reactions. FPRL2, the third member of this structural family of chemoattractant receptors, is characterized by its specific expression on monocytes and DCs. Here, we present the isolation from a spleen extract and the functional characterization of F2L, a novel chemoattractant peptide acting specifically through FPRL2. F2L is an acetylated amino-terminal peptide derived from the cleavage of the human heme-binding protein, an intracellular tetrapyrolle-binding protein. The peptide binds and activates FPRL2 in the low nanomolar range, which triggers intracellular calcium release, inhibition of cAMP accumulation, and phosphorylation of extracellular signal–regulated kinase 1/2 mitogen-activated protein kinases through the Gi class of heterotrimeric G proteins. When tested on monocytes and monocyte-derived DCs, F2L promotes calcium mobilization and chemotaxis. Therefore, F2L appears as a new natural chemoattractant peptide for DCs and monocytes, and the first potent and specific agonist of FPRL2.
Skip Nav Destination
Article navigation
3 January 2005
Article|
December 28 2004
Identification and characterization of an endogenous chemotactic ligand specific for FPRL2
Isabelle Migeotte,
Isabelle Migeotte
1Institut de Recherche en Biologie Humaine et Moléculaire, Université Libre de Bruxelles Campus Erasme, B-1070 Brussels, Belgium
Search for other works by this author on:
Elena Riboldi,
Elena Riboldi
3Section of General Pathology and Immunology, University of Brescia, 25121 Brescia, Italy
Search for other works by this author on:
Jean-Denis Franssen,
Jean-Denis Franssen
4Euroscreen s.a., B-6041 Gosselies, Belgium
Search for other works by this author on:
Françoise Grégoire,
Françoise Grégoire
2Laboratoire de Chimie Biologique et de la Nutrition, Université Libre de Bruxelles Campus Erasme, B-1070 Brussels, Belgium
Search for other works by this author on:
Cécile Loison,
Cécile Loison
4Euroscreen s.a., B-6041 Gosselies, Belgium
Search for other works by this author on:
Valérie Wittamer,
Valérie Wittamer
1Institut de Recherche en Biologie Humaine et Moléculaire, Université Libre de Bruxelles Campus Erasme, B-1070 Brussels, Belgium
Search for other works by this author on:
Michel Detheux,
Michel Detheux
4Euroscreen s.a., B-6041 Gosselies, Belgium
Search for other works by this author on:
Patrick Robberecht,
Patrick Robberecht
2Laboratoire de Chimie Biologique et de la Nutrition, Université Libre de Bruxelles Campus Erasme, B-1070 Brussels, Belgium
Search for other works by this author on:
Sabine Costagliola,
Sabine Costagliola
1Institut de Recherche en Biologie Humaine et Moléculaire, Université Libre de Bruxelles Campus Erasme, B-1070 Brussels, Belgium
Search for other works by this author on:
Gilbert Vassart,
Gilbert Vassart
1Institut de Recherche en Biologie Humaine et Moléculaire, Université Libre de Bruxelles Campus Erasme, B-1070 Brussels, Belgium
Search for other works by this author on:
Silvano Sozzani,
Silvano Sozzani
3Section of General Pathology and Immunology, University of Brescia, 25121 Brescia, Italy
5Istituto di Ricerche Farmacologiche Mario Negri, 20157 Milano, Italy
Search for other works by this author on:
Marc Parmentier,
Marc Parmentier
1Institut de Recherche en Biologie Humaine et Moléculaire, Université Libre de Bruxelles Campus Erasme, B-1070 Brussels, Belgium
Search for other works by this author on:
David Communi
David Communi
1Institut de Recherche en Biologie Humaine et Moléculaire, Université Libre de Bruxelles Campus Erasme, B-1070 Brussels, Belgium
Search for other works by this author on:
Isabelle Migeotte
1Institut de Recherche en Biologie Humaine et Moléculaire, Université Libre de Bruxelles Campus Erasme, B-1070 Brussels, Belgium
Elena Riboldi
3Section of General Pathology and Immunology, University of Brescia, 25121 Brescia, Italy
Jean-Denis Franssen
4Euroscreen s.a., B-6041 Gosselies, Belgium
Françoise Grégoire
2Laboratoire de Chimie Biologique et de la Nutrition, Université Libre de Bruxelles Campus Erasme, B-1070 Brussels, Belgium
Cécile Loison
4Euroscreen s.a., B-6041 Gosselies, Belgium
Valérie Wittamer
1Institut de Recherche en Biologie Humaine et Moléculaire, Université Libre de Bruxelles Campus Erasme, B-1070 Brussels, Belgium
Michel Detheux
4Euroscreen s.a., B-6041 Gosselies, Belgium
Patrick Robberecht
2Laboratoire de Chimie Biologique et de la Nutrition, Université Libre de Bruxelles Campus Erasme, B-1070 Brussels, Belgium
Sabine Costagliola
1Institut de Recherche en Biologie Humaine et Moléculaire, Université Libre de Bruxelles Campus Erasme, B-1070 Brussels, Belgium
Gilbert Vassart
1Institut de Recherche en Biologie Humaine et Moléculaire, Université Libre de Bruxelles Campus Erasme, B-1070 Brussels, Belgium
Silvano Sozzani
3Section of General Pathology and Immunology, University of Brescia, 25121 Brescia, Italy
5Istituto di Ricerche Farmacologiche Mario Negri, 20157 Milano, Italy
Marc Parmentier
1Institut de Recherche en Biologie Humaine et Moléculaire, Université Libre de Bruxelles Campus Erasme, B-1070 Brussels, Belgium
David Communi
1Institut de Recherche en Biologie Humaine et Moléculaire, Université Libre de Bruxelles Campus Erasme, B-1070 Brussels, Belgium
CORRESPONDENCE Marc Parmentier: [email protected]
Abbreviations used: ERK, extracellular signal–regulated kinase; FPR, formyl peptide receptor; FPRL, FPR-like receptor; GPCR, G protein–coupled receptor; HBP, heme-binding protein; MAP, mitogen-activated protein; SEC, size-exclusion column.
Received:
June 25 2004
Accepted:
November 22 2004
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2005
J Exp Med (2005) 201 (1): 83–93.
Article history
Received:
June 25 2004
Accepted:
November 22 2004
Citation
Isabelle Migeotte, Elena Riboldi, Jean-Denis Franssen, Françoise Grégoire, Cécile Loison, Valérie Wittamer, Michel Detheux, Patrick Robberecht, Sabine Costagliola, Gilbert Vassart, Silvano Sozzani, Marc Parmentier, David Communi; Identification and characterization of an endogenous chemotactic ligand specific for FPRL2 . J Exp Med 3 January 2005; 201 (1): 83–93. doi: https://doi.org/10.1084/jem.20041277
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionSuggested Content
Email alerts
Advertisement