MIP-3alpha, MIP-3beta and fractalkine induce the locomotion and the mobilization of intracellular calcium, and activate the heterotrimeric G proteins in human natural killer cells.
We demonstrate here that the CC chemokines macrophage inflammatory protein-3alpha (MIP-3alpha), macrophage inflammatory protein-3beta (MIP-3beta) and the CX3C chemokine fractalkine induce the chemotaxis of interleukin-2 (IL-2)-activated natural killer (IANK) cells. In addition, these chemokines enhance the binding of [gamma-35S]guanine triphosphate ([gamma-35S]GTP) to IANK cell membranes, suggesting that receptors for these chemokines are G protein-coupled. Our results show that MIP-3alpha receptors are coupled to Go, Gq and Gz, MIP-3beta receptors are coupled to Gi, Gq and Gs, whereas fractalkine receptors are coupled to Gi, and Gz. All three chemokines induced a robust calcium response flux in IANK cells. Cross-desensitization experiments show that MIP-3alpha, MIP-3beta or fractalkine use receptors not shared by each other or by the CC chemokine regulated on activation, normal, T-cell expressed, and secreted (RANTES), the CXC chemokines stromal-derived factor-1alpha (SDF-1alpha) and interferon-inducible protein-10 (IP-10), or the C chemokine lymphotactin.
Al-Aoukaty
A
A
Department of Anatomy, University of Oslo, Oslo, Norway.
Rolstad
B
B
Giaid
A
A
Maghazachi
A A
AA
D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D054415:Chemokine CCL19; D054418:Chemokine CCL20; D054428:Chemokine CX3CL1; D019742:Chemokines, CC / Q000494:pharmacology*; D020523:Chemokines, CX3C; D019743:Chemokines, CXC / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D008565:Membrane Proteins / Q000494:pharmacology; D054399:Receptors, CCR6; D019707:Receptors, Chemokine
C515460:CCL19 protein, human; C108355:CCL20 protein, human; C106311:CCR6 protein, human; C515538:CX3CL1 protein, human; D054415:Chemokine CCL19; D054418:Chemokine CCL20; D054428:Chemokine CX3CL1; D019742:Chemokines, CC; D020523:Chemokines, CX3C; D019743:Chemokines, CXC; D019402:Macrophage Inflammatory Proteins; D008565:Membrane Proteins; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D019204:GTP-Binding Proteins; D002118:Calcium