A seven-transmembrane, G protein–coupled receptor, FPRL1, mediates the chemotactic activity of serum amyloid A for human phagocytic cells

SB Su, W Gong, JL Gao, W Shen, PM Murphy… - The Journal of …, 1999 - rupress.org
SB Su, W Gong, JL Gao, W Shen, PM Murphy, JJ Oppenheim, JM Wang
The Journal of experimental medicine, 1999rupress.org
We have previously reported (Badolato, R., JM Wang, WJ Murphy, AR Lloyd, DF Michiel, LL
Bausserman, DJ Kelvin, and JJ Oppenheim. 1994. J. Exp. Med. 180: 203; Xu, L., R.
Badolato, WJ Murphy, DL Longo, M. Anver, S. Hale, JJ Oppenheim, and JM Wang. 1995. J.
Immunol. 155: 1184.) 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 …
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. 180:203; Xu, L., R. Badolato, W.J. Murphy, D.L. Longo, M. Anver, S. Hale, J.J. Oppenheim, and J.M. Wang. 1995. J. Immunol. 155:1184.) 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 chemoattrctants. 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.
rupress.org