Human resting CD16-, CD16+ and IL-2-, IL-12-, IL-15- or IFN-alpha-activated natural killer cells differentially respond to sphingosylphosphorylcholine, lysophosphatidylcholine and platelet-activating factor

Abstract

The phosphorylcholine-containing lipid lysophosphatidylcholine (LPC) is abundant in the bloodstream, whereas sphingosylphosphorylcholine (SPC) and platelet-activating factor (PAF) highly accumulate at inflamed sites. Utilizing RT-PCR, flow cytometry and immunoblot analyses, we show for the first time that ovarian cancer G protein-coupled receptor 1, the receptor for SPC, is expressed in IL-2-, IL-12- and IL-15-activated but not in resting CD16-, resting CD16+ or IFN-alpha-activated NK cells. Similarly, G2 accumulation and PAF receptor are variably expressed in these subsets of NK cells. SPC, LPC and PAF differentially induce the chemotaxis of resting and activated NK cells. In the chemotaxis assay, it is observed that resting CD16-CD56bright and CD16+CD56dim cells predominantly respond to LPC, whereas activated NK cells, regardless of the sort of stimulus, robustly respond to PAF. SPC is also a potent chemoattractant for IL-2-, IL-12- and IL-15- but not for IFN-alpha-activated NK cells. Further analysis shows that, depending on the cytokine pattern of NK cell activation, phosphorylcholine-containing lipids differentially affect IFN-gamma secretion by these cells. Our results provide one possible explanation for the tissue compartmentation of NK cells and their ability to secrete IFN-gamma. Furthermore, these results may provide novel information regarding NK cell regulation during inflammation.