C-C CHEMOKINES INDUCE THE CHEMOTAXIS OF NK AND IL-2-ACTIVATED NK CELLS - ROLE FOR G-PROTEINS

The C-C chemokines MIP-1 alpha, MCP-1, and RANTES, but not MIP-1 beta, induce the chemotaxis of NK and IL-2-activated NK (IANK) cells, as de termined in microchemotaxis assay. Only RANTES and MCP-1, but not MIP- 1 alpha were able to induce the chemokinesis of NK cells, In contrast, none of the C-C chemokines tested was able to induce the chemokinesis of IANK cells. IANK cell chemotaxis in response to MCP-1 or RANTES bu t not MIP-1 alpha, was inhibited by pertussis toxin (PT). In contrast, cholera toxin (CT) inhibited the ability of all three chemokines to i nduce the chemotaxis of IANK cells. IANK cells intoxicated with PT los t their ability to migrate in response to RANTES and MCP-1 but not MIP -1 alpha, whereas those intoxicated with CT lost their ability to migr ate in response to the three C-C chemokines tested. These results sugg est that gu ani ne nucleotide binding (G) proteins are coupled to C-C chemokine receptors in IANK cells. Subsequently, we observed that MIP- 1 alpha, MCP-1, and RANTES, but not MIP-1 beta, enhance the binding of guanosine 5'-O-(thiotriphosphate), and increase the hydrolysis of [P- 32]GTP in IANK cell membranes. Further analysis showed that MIP-1 alph a, RANTES, or MCP-1 did not enhance GTP binding in membranes prepared from IANK cells intoxicated with CT, whereas only RANTES and MCP-1 but not MIP-1 alpha lost their ability to enhance GTP binding to lANK cel l membranes prepared from PT-intoxicated cells. The differential inhib itory activity of CT and PT suggests that C-C chemokine receptors are coupled to different G proteins in IANK cells.