Functional Expression of Formyl Peptide Receptor Family in Human NK Cells

Abstract

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.

G-protein-coupled receptors in control of natural killer cell migration

“…However, many chemotactic compounds are not chemokines but other types of proteins, peptides or lipids. The expression on NK cells of functional chemotactic receptors for lysophosphatidic acid [78], leukotrienes [79], histamine [80], formylated peptides [81] has been described. They seem to induce NK cell chemotaxis in vitro but their role in NK cell trafficking in vivo has not been investigated.…”

Formylpeptide receptor 1 mediates the tumorigenicity of human hepatocellular carcinoma cells

“…Since FPR1 has been reported to mediate phosphorylation of MAP kinases in various cell types, [22][23][24] we stimulated serumstarved HepG2 and Hep3B cells with 100 nM fMLF and determined MAPK phosphorylation at different time points. fMLF stimulated ERK1/2 phosphorylation with a maximum effect at 5 min.…”

Comparative analysis of Annexin A1-formyl peptide receptor 2/ALX expression in human leukocyte subsets

“…These receptors recognize a wide variety of structurally unrelated natural and synthetic ligands including the arylcarboxylic acid hydrazide AG-14, the cheno/deoxycholic acid CDCA/DCA, aspirinInternational Immunopharmacology 11 (2011) [55][56][57][58][59][60][61][62][63][64][65][66] triggered lipoxin (ALX), the LL-37 and CCL23β peptides, serum amyloid A (SAA) and the name-giving agonist peptide fMLP [26][27][28]. Seminal studies by Walter et al and other studies have identified the N-terminus derived AnxA1 peptide Ac.2-26 as a ligand for FPR1 [29][30][31].…”