title: C-C chemokines induce the chemotaxis of NK and IL-2-activated NK cells. Role for G proteins.
abstract: 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 determined 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 but not MIP-1 alpha, was inhibited by pertussis toxin (PT). In contrast, cholera toxin (CT) inhibited the ability of all three chemokines to induce the chemotaxis of IANK cells. IANK cells intoxicated with PT lost 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 migrate in response to the three C-C chemokines tested. These results suggest that guanine 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 [32P]GTP in IANK cell membranes. Further analysis showed that MIP-1 alpha, 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 IANK cell membranes prepared from PT-intoxicated cells. The differential inhibitory activity of CT and PT suggests that C-C chemokine receptors are coupled to different G proteins in IANK cells.
authors.affiliation: Northeastern Ontario Regional Cancer Centre, Sudbury, Canada.
authors.forename: A A
authors.initials: AA
authors.lastname: Maghazachi
authors.forename: A
authors.initials: A
authors.lastname: al-Aoukaty
authors.forename: T J
authors.initials: TJ
authors.lastname: Schall
mesh_terms: D001427:Bacterial Toxins / Q000633:toxicity; D002460:Cell Line; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D002630:Chemotactic Factors / Q000037:antagonists & inhibitors / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000276:immunology*; D020558:GTP Phosphohydrolases / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology*; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008222:Lymphokines / Q000276:immunology; D019402:Macrophage Inflammatory Proteins; D015846:Monokines / Q000276:immunology
chemical_list: D001427:Bacterial Toxins; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D002630:Chemotactic Factors; D016207:Cytokines; D007376:Interleukin-2; D008222:Lymphokines; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D006160:Guanosine Triphosphate; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins