Interferon-inducible protein-10 and lymphotactin induce the chemotaxis and mobilization of intracellular calcium in natural killer cells through pertussis toxin-sensitive and -insensitive heterotrimeric G-proteins.
We show here that interferon-inducible protein-10 (IP-10), an ELR lacking CXC chemokine, and the C chemokine lymphotactin (Ltn) induce the chemotaxis and calcium mobilization in IL2-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 CXC chemokines. The chemotaxis induced by either IP-10 or Ltn for both cell 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 toxin. These results suggest important roles for PT-sensitive and -insensitive G-proteins in IP-10-induced and Ltn-induced chemotaxis and calcium fluxes in activated NK cells. This was further implicated after streptolysin O permeabilization of CHAK and IANK cells and after introduction of inhibitory antibodies to the PT-sensitive Gi and Go or the PT-insensitive Gq. Our results suggest that IP-10 and Ltn receptors are coupled to Gi, Go, and Gq in IANK cells and to Gi and Gq in CHAK cells, with a possible low coupling of IP-10, but not of Ltn, receptors to Go in these cells. Together, these results show that IP-10 and Ltn-dependent chemotaxis and calcium mobilization may differentiate at the level of receptor coupling to the heterotrimeric G-proteins.
Maghazachi
A A
AA
Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, Norway.
Skalhegg
B S
BS
Rolstad
B
B
Al-Aoukaty
A
A
D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000502:physiology; D054357:Chemokine CXCL10; D018925:Chemokines / Q000502:physiology*; D019744:Chemokines, C; D019743:Chemokines, CXC; D002634:Chemotaxis, Leukocyte; D003593:Cytoplasm / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D007158:Immunologic Techniques; D007694:Killer Cells, Natural / Q000502:physiology*; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000494:pharmacology*; D037342:Pertussis Toxin; D011956:Receptors, Cell Surface / Q000502:physiology; D011971:Receptors, Immunologic / Q000502:physiology; D015290:Second Messenger Systems; D012795:Sialoglycoproteins / Q000494:pharmacology*; D015398:Signal Transduction; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D018925:Chemokines; D019744:Chemokines, C; D019743:Chemokines, CXC; D008222:Lymphokines; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D012795:Sialoglycoproteins; D010566:Virulence Factors, Bordetella; C092390:XCL1 protein, human; C018997:lymphotactin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D002118:Calcium