QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bae, Y.-S. Articles by Ho Ryu, S. Search for Related Content PubMed PubMed Citation Articles by Bae, Y.-S. Articles by Ho Ryu, S.

Differential Signaling of Formyl Peptide Receptor-Like 1 by Trp-Lys-Tyr-Met-Val-Met-CONH₂ or Lipoxin A4 in Human Neutrophils

Medical Research Center for Cancer Molecular Therapy and Department of Biochemistry College of Medicine, Dong-A University, Busan, Korea (Y.-S.B., J.-Y.K.); Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, Korea (J.C.P., P.-G.S., S.H.R.); and Department of Pharmacology, University of Illinois, Chicago, Illinois (R.H., R.D.Y.).

Classical chemoattractant receptors are of fundamental importance to immune responses. The two major roles of such receptors are the modulation of chemotaxis and the generation of reactive oxygen species. The formyl peptide receptor-like 1 (FPRL1) can be stimulated by two different ligands, Trp-Lys-Tyr-Met-Val-Met-CONH₂ (WKYMVM) and lipoxin A4 (LXA4). Although leukocyte chemotaxis mediated by activated FPRL1 has been reported, the role of FPRL1 in superoxide generation remains to be studied. In this study, we examined the effect of WKYMVM or LXA4 on chemotactic migration and superoxide generation in human neutrophils. WKYMVM and LXA4 stimulated neutrophil chemotaxis via tyrosine phosphorylation events. In terms of reactive oxygen species generation, WKYMVM but not LXA4 stimulated superoxide generation in neutrophils. To understand this difference on superoxide generation via the same receptor, FPRL1, we compared the signaling pathways downstream of FPRL1 by the two different ligands. At first, we confirmed that both WKYMVM and LXA4 caused intracellular calcium ([Ca²⁺]_i) increase in a pertussis toxin-sensitive manner and that these ligands competitively inhibited each other with respect to [Ca²⁺]_i increase in neutrophils. This result suggests that WKYMVM and LXA4 share the same receptor, FPRL1. By investigating cellular signaling by WKYMVM and LXA4, we found that WKYMVM but not LXA4 induced extracellular signal-regulated protein kinases (ERKs), c-Jun NH₂-terminal kinase, and phospholipase A₂ (PLA₂) activation. We also found that ERK-mediated cytosolic PLA₂ activity is essential for superoxide generation. These results indicate that the activation of FPRL1 by the two different ligands can induce differential cellular signaling and unique functional consequences in human neutrophils.

Address correspondence to: Sung Ho Ryu, Ph.D., Division of Molecular and Life Sciences, Pohang University of Science and Technology, San 31, Hyojadong, Pohang, 790-784, Korea. E-mail: sungho{at}postech.ac.kr

This article has been cited by other articles:

				C. Prat, J. Bestebroer, C. J. C. de Haas, J. A. G. van Strijp, and K. P. M. van Kessel A New Staphylococcal Anti-Inflammatory Protein That Antagonizes the Formyl Peptide Receptor-Like 1 J. Immunol., December 1, 2006; 177(11): 8017 - 8026. [Abstract] [Full Text] [PDF]

				I. Nagaoka, H. Tamura, and M. Hirata An Antimicrobial Cathelicidin Peptide, Human CAP18/LL-37, Suppresses Neutrophil Apoptosis via the Activation of Formyl-Peptide Receptor-Like 1 and P2X7. J. Immunol., March 1, 2006; 176(5): 3044 - 3052. [Abstract] [Full Text] [PDF]

				M. Nanamori, X. Cheng, J. Mei, H. Sang, Y. Xuan, C. Zhou, M.-W. Wang, and R. D. Ye A Novel Nonpeptide Ligand for Formyl Peptide Receptor-Like 1 Mol. Pharmacol., November 1, 2004; 66(5): 1213 - 1222. [Abstract] [Full Text] [PDF]

				M. Lenoir, B. Djerdjouri, and A. Perianin Stroma Cell-Derived Factor 1{alpha} Mediates Desensitization of Human Neutrophil Respiratory Burst in Synovial Fluid from Rheumatoid Arthritic Patients J. Immunol., June 1, 2004; 172(11): 7136 - 7143. [Abstract] [Full Text] [PDF]