Functional expression of formyl peptide receptor family in human NK cells.
We determined the expression of the formyl peptide receptor (FPR) family and the functional roles of the FPR family in NK cells. All tested human NK cells express two members of the FPR family (FPR1 and FPR2). The expression of FPR3 was noted to occur in a donor-specific manner. The stimulation of NK cells with FPR family-selective agonists (fMLF (N-formyl-Met-Leu-Phe), MMK-1, F2L, and WKYMVm (Trp-Lys-Tyr-Met-Val-d-Met)) elicited cytolytic activity in resting NK cells, but not in IL-2-activated NK cells; the cytolytic activity was not inhibited by pertussis toxin. The FPR family agonists also stimulated chemotactic migration of IL-2-activated NK cells, but not resting NK cells; the chemotactic migration was completely inhibited by pertussis toxin. WKYMVm stimulates ERK, p38 MAPK, and JNK activities in both resting and IL-2-activated NK cells. WKYMVm-induced chemotactic migration was partially inhibited by PD98059 (2'-amino-3'-methoxyflavone); however, the inhibition of JNK by its selective inhibitor (SP600125, anthra[1,9-cd]pyrazol-6(2H)-one) dramatically inhibited the WKYMVm-induced cytolytic activity. Furthermore, WKYMVm-induced chemotactic migration and cytolytic activity were partly inhibited by FPR family-selective antagonists (cyclosporin H and WRWWWW). Taken together, our findings indicate that human NK cells express functional members of the FPR family, and in turn the activation of the three members of the FPR receptor family elicit cytolytic activity in NK cells, thus suggesting that the receptors are potentially important therapeutic targets for the modulation of NK cell-mediated immune responses.
Kim
Sang Doo
SD
Department of Biochemistry, College of Medicine, Dong-A University, Busan, Korea.
Kim
Jung Mo
JM
Jo
Seong Ho
SH
Lee
Ha Young
HY
Lee
Sun Young
SY
Shim
Jae Woong
JW
Seo
Su-Kil
SK
Yun
Jeanho
J
Bae
Yoe-Sik
YS
D002634:Chemotaxis, Leukocyte / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D005810:Multigene Family / Q000276:immunology*; D009842:Oligopeptides / Q000819:agonists / Q000096:biosynthesis / Q000502:physiology; D044042:Receptors, Formyl Peptide / Q000819:agonists / Q000096:biosynthesis* / Q000502:physiology; D044067:Receptors, Lipoxin / Q000819:agonists / Q000096:biosynthesis / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology
C469986:FPR1 protein, human; C105101:FPR2 protein, human; C469985:FPR3 protein, human; D009842:Oligopeptides; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; C113617:Trp-Lys-Tyr-Met-Val-Met