The Journal of Experimental Medicine
Avanti Polar Lipids, Inc.
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© The Rockefeller University Press, 0022-1007/1999/1/395/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 2, January 18, 1999 395-402

Articles

A Seven-transmembrane, G Protein–coupled Receptor, FPRL1, Mediates the Chemotactic Activity of Serum Amyloid A for Human Phagocytic Cells

Shao Bo Su*, Wanghua Gong{ddagger}, Ji-Liang Gao§, Weiping Shen*, Philip M. Murphy§, Joost J. Oppenheim*, and Ji Ming Wang*

From the * Laboratory of Molecular Immunoregulation, Division of Basic Sciences; the {ddagger} Intramural Research Support Program, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201; and the § Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892

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.

Key Words: serum amyloid A • FPRL1 • chemotaxis • calcium flux • receptor

Address correspondence to Ji Ming Wang, LMI, DBS, NCI-FCRDC, Bldg. 560, Rm. 31-40, Frederick, MD 21702. Phone: 301-846-5454; Fax: 301-846-7042; E-mail: wangji{at}mail.ncifcrf.gov

The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.

S.B. Su and W. Shen are supported in part by a fellowship from the Office of the International Affairs, National Cancer Institute, National Institutes of Health (NCI, NIH). This project has been funded in part with Federal funds from the NCI under contract No. NO1-CO-56000.

Abbreviations used: CI, chemotaxis indexes; EC, effective concentration; fMLP, N-formyl-methionyl-leucyl-phenylalanine; HDL, high density lipoprotein; LXA4, lipoxin A4; SAA, serum amyloid A.


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