Regulation of S100A8/A9 (Calprotectin) Binding to Tumor Cells by Zinc Ion and Its Implication for Apoptosis-Inducing Activity
S100A8/A9 (calprotectin), which is released by neutrophils under inflammatory conditions, has the capacity to induce apoptosis in various cells. We previously reported that S100A8/A9 induces apoptosis of EL-4 lymphoma cells via the uptake of extracellular zinc in a manner similar to DTPA, a membrane...
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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2005-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/MI.2005.280 |
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| Summary: | S100A8/A9 (calprotectin), which is released by neutrophils under
inflammatory conditions, has the capacity to induce apoptosis in
various cells. We previously reported that S100A8/A9 induces
apoptosis of EL-4 lymphoma cells via the uptake of extracellular
zinc in a manner similar to DTPA, a membrane-impermeable zinc
chelator. In this study, S100A8/A9-induced apoptosis was examined
in several cell lines that are weakly sensitive to DTPA,
suggesting S100A8/A9 is directly responsible for apoptosis in
these cells. Since zinc inhibits apoptosis of MM46, one of these
cells, the regulation by zinc of the capacity of S100A8/A9 to bind
MM46 cells was studied. When MM46 cells were incubated with
S100A8/A9 in standard or zinc-depleted medium, the amounts of
S100A8/A9 bound to cells was markedly lower at 3 h than at
1 h. In contrast, when MM46 cells were incubated with
S100A8/A9 in the presence of high levels of zinc, binding to cells
was the same at 1 and 3 h. When the cells were permeabilized
with saponin prior to analysis, a larger amount of cell-associated
S100A8/A9 was detected at 3 h. The amount was further
increased in cells treated with chloroquine, suggesting that
S100A8/A9 was internalized and degraded in lysosomes. Although it
has been reported that S100A8/A9 binds to heparan sulfate on cell
membranes, the amount of S100A8/A9 bound to MM46 cells was not
reduced by heparinase treatment, but was reduced by trypsin
treatment. These results suggest that S100A8/A9 induces apoptosis by
direct binding to MM46 cells, and that this activity is regulated
by zinc. |
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| ISSN: | 0962-9351 1466-1861 |