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*
Laboratory of Molecular Immunoregulation, Division of Basic Sciences, National Cancer Institute-Frederick Cancer Research and Development Center and
Intramural Research Support Program, Science Applications International Corp.-Frederick, Frederick, MD 21702; and
Department of Pharmacology, University of Illinois, Chicago, IL 60612
Trp-Lys-Tyr-Val-D-Met (WKYMVm) is a synthetic leukocyte-activating peptide postulated to use seven-transmembrane, G protein-coupled receptor(s). In the study to characterize the receptor(s) for WKYMVm, we found that this peptide induced marked chemotaxis and calcium flux in human phagocytes. The signaling induced by WKYMVm in phagocytes was attenuated by high concentrations of the bacterial chemotactic peptide fMLP, suggesting that WKYMVm might use receptor(s) for fMLP. This hypothesis was tested by using cells over expressing genes encoding two seven-transmembrane receptors, formyl peptide receptor (FPR) and formyl peptide receptor-like 1 (FPRL1), which are with high and low affinity for fMLP, respectively. Both FPR- and FPRL1-expressing cells mobilized calcium in response to picomolar concentrations of WKYMVm. While FPRL1-expressing cells migrated to picomolar concentrations of WKYMVm, nanomolar concentrations of the peptide were required to induce migration of FPR-expressing cells. In contrast, fMLP elicited both calcium flux and chemotaxis only in FPR-expressing cells with an efficacy comparable with WKYMVm. Thus, WKYMVm uses both FPR and FPRL1 to stimulate phagocytes with a markedly higher efficacy for FPRL1. Our study suggests that FPR and FPRL1 in phagocytes react to a broad spectrum of agonists and WKYMVm as a remarkably potent agonist provides a valuable tool for studying leukocyte signaling via these receptors.
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H. YAZAWA, Z.-X. YU, TAKEDA, Y. LE, W. GONG, V. J. FERRANS, J. J. OPPENHEIM, C. C. H. LI, and J. M. WANG {beta} Amyloid peptide (A{beta}42) is internalized via the G-protein-coupled receptor FPRL1 and forms fibrillar aggregates in macrophages FASEB J, November 1, 2001; 15(13): 2454 - 2462. [Abstract] [Full Text] [PDF]
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J. Y. Hu, Y. Le, W. Gong, N. M. Dunlop, J. L. Gao, P. M. Murphy, and J. M. Wang Synthetic peptide MMK-1 is a highly specific chemotactic agonist for leukocyte FPRL1 J. Leukoc. Biol., July 1, 2001; 70(1): 155 - 161. [Abstract] [Full Text] [PDF]
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D. L. Jaye, H. A. Edens, L. Mazzucchelli, and C. A. Parkos Novel G Protein-Coupled Responses in Leukocytes Elicited by a Chemotactic Bacteriophage Displaying a Cell Type-Selective Binding Peptide J. Immunol., June 15, 2001; 166(12): 7250 - 7259. [Abstract] [Full Text] [PDF]
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M. Yang, H. Sang, A. Rahman, D. Wu, A. B. Malik, and R. D. Ye G{{alpha}}16 Couples Chemoattractant Receptors to NF-{{kappa}}B Activation J. Immunol., June 1, 2001; 166(11): 6885 - 6892. [Abstract] [Full Text] [PDF]
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B.-Q. Li, M. A. Wetzel, J. A. Mikovits, E. E. Henderson, T. J. Rogers, W. Gong, Y. Le, F. W. Ruscetti, and J. M. Wang The synthetic peptide WKYMVm attenuates the function of the chemokine receptors CCR5 and CXCR4 through activation of formyl peptide receptor-like 1 Blood, May 15, 2001; 97(10): 2941 - 2947. [Abstract] [Full Text] [PDF]
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Y.-S. Bae, H. Bae, Y. Kim, T. G. Lee, P.-G. Suh, and S. H. Ryu Identification of novel chemoattractant peptides for human leukocytes Blood, May 1, 2001; 97(9): 2854 - 2862. [Abstract] [Full Text] [PDF]
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D. Yang, Q. Chen, Y. Le, J. M. Wang, and J. J. Oppenheim Differential Regulation of Formyl Peptide Receptor-Like 1 Expression During the Differentiation of Monocytes to Dendritic Cells and Macrophages J. Immunol., March 15, 2001; 166(6): 4092 - 4098. [Abstract] [Full Text] [PDF]
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R. He, D. D. Browning, and R. D. Ye Differential Roles of the NPXXY Motif in Formyl Peptide Receptor Signaling J. Immunol., March 15, 2001; 166(6): 4099 - 4105. [Abstract] [Full Text] [PDF]
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Y. Le, H. Yazawa, W. Gong, Z. Yu, V. J. Ferrans, P. M. Murphy, and J. M. Wang Cutting Edge: The Neurotoxic Prion Peptide Fragment PrP106-126 Is a Chemotactic Agonist for the G Protein-Coupled Receptor Formyl Peptide Receptor-Like 1 J. Immunol., February 1, 2001; 166(3): 1448 - 1451. [Abstract] [Full Text] [PDF]
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R. He, L. Tan, D. D. Browning, J. M. Wang, and R. D. Ye The Synthetic Peptide Trp-Lys-Tyr-Met-Val-D-Met Is a Potent Chemotactic Agonist for Mouse Formyl Peptide Receptor J. Immunol., October 15, 2000; 165(8): 4598 - 4605. [Abstract] [Full Text] [PDF]
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De Yang, Q. Chen, A. P. Schmidt, G. M. Anderson, J. M. Wang, J. Wooters, J. J. Oppenheim, and O. Chertov Ll-37, the Neutrophil Granule-And Epithelial Cell-Derived Cathelicidin, Utilizes Formyl Peptide Receptor-Like 1 (Fprl1) as a Receptor to Chemoattract Human Peripheral Blood Neutrophils, Monocytes, and T Cells J. Exp. Med., October 2, 2000; 192(7): 1069 - 1074. [Abstract] [Full Text] [PDF]
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T. Christophe, A. Karlsson, C. Dugave, M.-J. Rabiet, F. Boulay, and C. Dahlgren The Synthetic Peptide Trp-Lys-Tyr-Met-Val-Met-NH2 Specifically Activates Neutrophils through FPRL1/Lipoxin A4 Receptors and Is an Agonist for the Orphan Monocyte-expressed Chemoattractant Receptor FPRL2 J. Biol. Chem., June 8, 2001; 276(24): 21585 - 21593. [Abstract] [Full Text] [PDF]
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