Differential utilization of cyclic ADP-ribose pathway by chemokines to induce the mobilization of intracellular calcium in NK cells.
We show here that cyclic adenosine diphosphate-ribose (cADPR) may be a second messenger for chemokines. Extracts collected from NK cells stimulated with IL-8 for 2 min were incubated with beta-NAD for an additional 2 min (designated as IL-8 extracts). This mixture elevated the mobilization of (Ca(2+))(i) in alpha-toxin permeabilized NK cells. This activity was inhibited upon prior incubation of these cells with ruthenium red but not with heparin. Purified cADPR and not Ins 1,4,5 P(3) desensitized NK cells to the calcium mobilization effect of IL-8 extracts. Further analysis showed that ruthenium red and heparin differentially inhibit RANTES-, SDF-1alpha-, or MDC-induced calcium mobilization in IL-2-activated NK cells. Also, introduction of anti-ryanodine receptor antibody inside streptolysin O-permeabilized NK cells resulted in complete inhibition of MDC, and only partial inhibition of RANTES and SDF-1alpha-induced calcium fluxes in NK cells. Collectively, these results suggest that chemokines may utilize the cADPR/ryanodine receptor pathway as well as the Ins 1,4,5 P(3)/Ins 1,4,5 P(3) receptor signaling pathway to induce the accumulation of calcium in NK cells.
Inngjerdingen
M
M
Institute of Basic Medical Sciences, University of Oslo, Oslo, N-0317, Norway.
Al-Aoukaty
A
A
Damaj
B
B
Maghazachi
A A
AA
D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D002463:Cell Membrane Permeability; D054422:Chemokine CCL22; D018946:Chemokine CCL5; D054377:Chemokine CXCL12; D018925:Chemokines / Q000378:metabolism*; D019742:Chemokines, CC; D019743:Chemokines, CXC; D036563:Cyclic ADP-Ribose; D006493:Heparin; D015544:Inositol 1,4,5-Trisphosphate; D053496:Inositol 1,4,5-Trisphosphate Receptors; D016209:Interleukin-8 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D012430:Ruthenium Red; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D015290:Second Messenger Systems; D010738:Type C Phospholipases
D015220:Calcium Channels; D054422:Chemokine CCL22; D018946:Chemokine CCL5; D054377:Chemokine CXCL12; D018925:Chemokines; D019742:Chemokines, CC; D019743:Chemokines, CXC; D053496:Inositol 1,4,5-Trisphosphate Receptors; D016209:Interleukin-8; D018160:Receptors, Cytoplasmic and Nuclear; D019837:Ryanodine Receptor Calcium Release Channel; D012430:Ruthenium Red; D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose; D015544:Inositol 1,4,5-Trisphosphate; D006493:Heparin; D010738:Type C Phospholipases; D002118:Calcium