Expression and regulation of chemokine receptors in human natural killer cells

Using flow cytometric and RNase protection assays, this study examined the expression of chemokine receptors in nonactivated natural killer (NK) cells and compared this expression with NK cells activated with interleukin (IL) -2, which either adhered to plastic flasks (AD) or did not adhere (NA), Non e of the NK cell subsets expressed CXCR2, CXCR5, or CCR5, The major differe nces between these cells include increased expression of CXCR1, CCR1, CCR2, CCR4, CCR8, and CX(3)CR1 in AD when compared to NA or nonactivated NK cell s. The chemotactic response to the CXC and CC chemokines correlated with th e receptor expression except that all 3 populations responded to GRO-alpha, despite their lack of CXCR2 expression. Pretreatment of these cells with a nti-CXCR2 did not inhibit the chemotactic response to GRO-alpha, In additio n, nonactivated and NA cells responded to fractalkine, although they lack t he expression of CX(3)CR1. This activity was not inhibited by anti-CX(3)CR1 . Viral macrophage inflammatory protein (vMIP)-I, I-309, and TARC competed with the binding of I-125-309 to AD cells with varying affinities. Transfor ming growth factor(TGF)-beta1 but not any other cytokine or chemokine exami ned including interferon (IFN)-gamma, MIP-3 beta, macrophage-derived chemok ine (MDC), thymus and activation-regulated chemokine (TARC) or I-309, up-re gulated the expression of CXCR3 and CXCR4 on NK cell surface. This is corre lated with increased chemotaxis of NK cells treated with TGF-beta1 toward s tromal cell-derived factor (SDF)-1 alpha and interferon-inducible protein-i n (IP-10), Messenger RNA for lymphotactin, RANTES, MIP-1 alpha, and MIP-1 b eta, but not IP-10, monocyte chemotactic protein (MCP)-1, IL-8, or I-309 wa s expressed in all 3 NK cell subsets. Our results may have implications for the dissemination of NK cells at the sites of tumor growth or viral replic ation. (C) 2001 by The American Society of Hematology.