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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| Format: | Article |
| Language: | English |
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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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| author | Yuichi Nakatani Masatoshi Yamazaki Walter J. Chazin Satoru Yui |
| author_facet | Yuichi Nakatani Masatoshi Yamazaki Walter J. Chazin Satoru Yui |
| author_sort | Yuichi Nakatani |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-1788972ddb434170be402f16b064ff7a |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2005-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-1788972ddb434170be402f16b064ff7a2025-02-03T05:53:36ZengWileyMediators of Inflammation0962-93511466-18612005-01-012005528029210.1155/MI.2005.280Regulation of S100A8/A9 (Calprotectin) Binding to Tumor Cells by Zinc Ion and Its Implication for Apoptosis-Inducing ActivityYuichi Nakatani0Masatoshi Yamazaki1Walter J. Chazin2Satoru Yui3Faculty of Pharmaceutical Sciences, Teikyo University, 1091-1 Sagamiko, Tsukui-gun, Kanagawa, 199-0195, JapanFaculty of Pharmaceutical Sciences, Teikyo University, 1091-1 Sagamiko, Tsukui-gun, Kanagawa, 199-0195, JapanDepartments of Biochemistry and Physics, Center for Structural Biology, Vanderbilt University, Nashville 37232-8725, TN, USAFaculty of Pharmaceutical Sciences, Teikyo University, 1091-1 Sagamiko, Tsukui-gun, Kanagawa, 199-0195, JapanS100A8/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.http://dx.doi.org/10.1155/MI.2005.280 |
| spellingShingle | Yuichi Nakatani Masatoshi Yamazaki Walter J. Chazin Satoru Yui Regulation of S100A8/A9 (Calprotectin) Binding to Tumor Cells by Zinc Ion and Its Implication for Apoptosis-Inducing Activity Mediators of Inflammation |
| title | Regulation of S100A8/A9 (Calprotectin) Binding to Tumor Cells by
Zinc Ion and Its Implication for Apoptosis-Inducing Activity |
| title_full | Regulation of S100A8/A9 (Calprotectin) Binding to Tumor Cells by
Zinc Ion and Its Implication for Apoptosis-Inducing Activity |
| title_fullStr | Regulation of S100A8/A9 (Calprotectin) Binding to Tumor Cells by
Zinc Ion and Its Implication for Apoptosis-Inducing Activity |
| title_full_unstemmed | Regulation of S100A8/A9 (Calprotectin) Binding to Tumor Cells by
Zinc Ion and Its Implication for Apoptosis-Inducing Activity |
| title_short | Regulation of S100A8/A9 (Calprotectin) Binding to Tumor Cells by
Zinc Ion and Its Implication for Apoptosis-Inducing Activity |
| title_sort | regulation of s100a8 a9 calprotectin binding to tumor cells by zinc ion and its implication for apoptosis inducing activity |
| url | http://dx.doi.org/10.1155/MI.2005.280 |
| work_keys_str_mv | AT yuichinakatani regulationofs100a8a9calprotectinbindingtotumorcellsbyzincionanditsimplicationforapoptosisinducingactivity AT masatoshiyamazaki regulationofs100a8a9calprotectinbindingtotumorcellsbyzincionanditsimplicationforapoptosisinducingactivity AT walterjchazin regulationofs100a8a9calprotectinbindingtotumorcellsbyzincionanditsimplicationforapoptosisinducingactivity AT satoruyui regulationofs100a8a9calprotectinbindingtotumorcellsbyzincionanditsimplicationforapoptosisinducingactivity |