MIP-3 alpha, MIP-3 beta and fractalkine induce the locomotion and the mobilization of intracellular calcium, and activate the heterotrimeric G proteins in human natural killer cells

demonstrate here that the CC chemokines macrophage inflammatory protein-3 a lpha (MIP-3 alpha), macrophage inflammatory protein-3 beta (MIP-3 beta) and the CX3C chemokine fractalkine induce the chemotaxis of interleukin-2 (IL- 2)-activated natural killer (IANK) cells. In addition, these chemokines enh ance the binding of [gamma-S-35]guanine triphosphate ([gamma-S-35]GTP) to I ANK cell membranes, suggesting that receptors for these chemokines are G pr otein-coupled. Our results show that MIP-3 alpha receptors are coupled to G (o), G(q) and G(z), MIP-3 beta receptors are coupled to G(i), G(q) and G(s) , whereas fractaIkine receptors are coupled to G(i), and G(z). All three ch emokines induced a robust calcium response flux in IANK cells. Cross-desens itization experiments show that MIP-3 alpha, MIP-3 beta or fractalkine use receptors not shared by each other or by the CC chemokine regulated on acti vation, normal, T-cell expressed, and secreted (RANTES), the CXC chemokines stromal-derived factor-1 alpha (SDF-1 alpha) and interferon-inducible prot ein-10 (IP-10), or the C chemokine lymphotactin.