A seven-transmembrane, G protein-coupled receptor, FPRL1, mediates the chemotactic activity of serum amyloid A for human phagocytic cells.
J Exp Med
; 189(2): 395-402, 1999 Jan 18.
Article
en En
| MEDLINE
| ID: mdl-9892621
ABSTRACT
We have previously reported (Badolato, R., J.M. Wang, W.J. Murphy, A. R. Lloyd, D.F. Michiel, L.L. Bausserman, D.J. Kelvin, and J.J. Oppenheim. 1994. J. Exp. Med. 180203; Xu, L., R. Badolato, W.J. Murphy, D.L. Longo, M. Anver, S. Hale, J.J. Oppenheim, and J.M. Wang. 1995. J. Immunol. 1551184.) that the acute phase protein serum amyloid A (SAA) is a potent chemoattractant for human leukocytes in vitro and mouse phagocytes in vivo. To identify the signaling mechanisms, we evaluated patterns of cross-desensitization between SAA and other leukocyte chemoattractants. We found that the chemotactic bacterial peptide, N-formyl- methionyl-leucyl-phenylalanine (fMLP), was able to specifically attenuate Ca2+ mobilization in human phagocytes induced by SAA, but only at very high concentrations, suggesting that SAA uses a low affinity fMLP receptor. Here we demonstrate that SAA selectively induced Ca2+ mobilization and migration of HEK cells expressing FPRL1, a human seven-transmembrane domain phagocyte receptor with low affinity for fMLP, and high affinity for lipoxin A4. Furthermore, radiolabeled SAA specifically bound to human phagocytes and FPRL1-transfected 293 cells. In contrast, SAA was not a ligand or agonist for FPR, the high affinity fMLP receptor. Thus, SAA is the first chemotactic ligand identified for FPRL1. Our results suggest that FPRL1 mediates phagocyte migration in response to SAA.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Apolipoproteínas
/
Fagocitos
/
Proteína Amiloide A Sérica
/
Receptores Inmunológicos
/
Quimiotaxis
/
Receptores de Péptidos
/
Proteínas de Unión al GTP
/
Receptores de Lipoxina
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Exp Med
Año:
1999
Tipo del documento:
Article
País de afiliación:
Estados Unidos