INTERFERON-INDUCIBLE PROTEIN-10 AND LYMPHOTACTIN INDUCE THE CHEMOTAXIS AND MOBILIZATION OF INTRACELLULAR CALCIUM IN NATURAL-KILLER-CELLS THROUGH PERTUSSIS-TOXIN-SENSITIVE AND PERTUSSIS-TOXIN-INSENSITIVE HETEROTRIMERIC G-PROTEINS

We show here that interferon-inducible protein-10 (IP-10), an ELR lack ing CXC chemokine, and the C chemokine lymphotactin (Ltn) induce the c hemotaxis and calcium mobilization in IL-2-activated NK (IANK) and CC chemokine-activated NK (CHAK) cells. Cross-desensitization experiments show that IP-10 or Ltn use receptors not shared by other C, CC, or CX C chemokines. The chemotaxis induced by either IP-10 or Ltn for both c ell types is inhibited upon pretreatment of these cells with pertussis toxin (PT), Also, Ltn-induced [Ca2+](i) in IANK but not in CHAK cells is inhibited upon pretreatment with PT, whereas IP-10-induced [Ca2+]( i) in IANK and CHAK cells is inhibited upon pretreatment with this tox in, These results suggest important roles for PT-sensitive and -insens itive G-proteins in IP-10-induced and Ltn-induced chemotaxis and calci um fluxes in activated NK cells, This was further implicated after str eptolysin O permeabilization of CHAK and IANK cells and after introduc tion of inhibitory antibodies to the PT-sensitive G(i) and G(o) or the PT-insensitive G(q). Our results suggest that IP-10 and Ltn receptors are coupled to G(i), G(o), and G(q) in IANK cells and to G(i) and G(q ) in CHAX cells, with a possible low coupling of IP-10, but not of Ltn , receptors to G(o) in these cells, Together, these results show that IP-10 and Ltn-dependent chemotaxis and calcium mobilization may differ entiate at the level of receptor coupling to the heterotrimeric G-prot eins.