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Activation of CD38 by Interleukin-8 Signaling Regulates Intracellular Ca super(2+) Level and Motility of Lymphokine-activated Killer Cells

CD38 is an ADP-ribosyl cyclase, producing a potent Ca super(2+) mobilizer cyclic ADP-ribose (cADPR). In this study, we have investigated a role of CD38 and its regulation through interleukin-8 (IL8) signaling in lymphokine-activated killer (LAK) cells. Incubation of LAK cells with IL8 resulted in an...

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Bibliographic Details
Published in:The Journal of biological chemistry 2005-01, Vol.280 (4), p.2888-2895
Main Authors: Rah, So-Young, Park, Kwang-Hyun, Han, Myung-Kwan, Im, Mie-Jae, Kim, Uh-Hyun
Format: Article
Language:English
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Summary:CD38 is an ADP-ribosyl cyclase, producing a potent Ca super(2+) mobilizer cyclic ADP-ribose (cADPR). In this study, we have investigated a role of CD38 and its regulation through interleukin-8 (IL8) signaling in lymphokine-activated killer (LAK) cells. Incubation of LAK cells with IL8 resulted in an increase of cellular cADPR level and a rapid rise of intracellular Ca super(2+) concentration ([Ca super(2+)] sub(i)), which was sustained for a long period of time (>10 min). Preincubation of an antagonistic cADPR analog, 8-Br-cADPR (8-bromo-cyclic adenosine diphosphate ribose), abolished the sustained Ca super(2+) signal only but not the initial Ca super(2+) rise. An inositol 1,4,5-trisphosphate (IP sub(3)) receptor antagonist blocked both Ca super(2+) signals. Interestingly, the sustained Ca super(2+) rise was not observed in the absence of extracellular Ca super(2+). Functional CD38-null (CD38 super(-)) LAK cells showed the initial rapid increase of [Ca super(2+)] sub(i) but not the sustained Ca super(2+) rise in response to IL8 treatment. An increase of cellular cADPR level by cGMP analog, 8-pCPT-cGMP (8-(4-chlorophenylthio)-guanosine-3',5'-cyclic monophosphate), (4-chlorophenylthio)-guanosine-3',5'-cyclic monophosphate), but not cAMP analog or phorbol 12-myristate 13-acetate was observed. IL8 treatment resulted in the increase of cGMP level that was inhibited by the IP sub(3) receptor blocker but not a protein kinase C inhibitor. cGMP-mediated Ca super(2+) rise was blocked by 8- Br-cADPR. In addition, IL8-mediated LAK cell migration was inhibited by 8-Br- cADPR and a protein kinase G inhibitor. Consistent with these observations, IL8- induced migration of CD38 super(-) LAK cells was not observed. However, direct application of cADPR or 8-pCPT-cGMP stimulated migration of CD38 super(-) cells. These results demonstrate that CD38 is stimulated by sequential activation of IL8 receptor, IP sub(3)-mediated Ca super(2+) rise, and cGMP/protein kinase G and that CD38 plays an essential role in IL8-induced migration of LAK cells.
ISSN:0021-9258
1083-351X