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It is known that <jats:italic>S. pyogenes<\/jats:italic> CAMP factor induces vacuolation in macrophages; however, the mechanism remains unclear. In the current study, the mechanism by which CAMP factor induces vacuolation in macrophages was investigated. CAMP factor was found to induce calcium ion uptake in murine macrophage RAW264.7 cells. In addition, EDTA inhibited calcium ion uptake and vacuolation in the cells. The L\u2010type voltage\u2010dependent calcium ion channel blockers nifedipine and verapamil reduced vacuolation. Furthermore, the phosphoinositide 3\u2010kinase inhibitors LY294002 and wortmannin also inhibited the vacuolation induced by CAMP factor. Fluorescent microscopy revealed that clathrin localized to the vacuoles. These results suggest that the vacuolation is related to calcium ion uptake by RAW264.7 cells via L\u2010type voltage\u2010dependent calcium ion channels. Therefore, it was concluded that the vacuoles induced by <jats:italic>S. pyogenes<\/jats:italic> CAMP factor in macrophages are clathrin\u2010dependent endosomes induced by activation of the phosphoinositide 3\u2010kinase signaling pathway through calcium ion uptake.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1348-0421.12647","type":"journal-article","created":{"date-parts":[[2018,9,13]],"date-time":"2018-09-13T13:09:08Z","timestamp":1536844148000},"page":"617-623","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<i>Streptococcus pyogenes<\/i> CAMP factor promotes calcium ion uptake in RAW264.7 cells"],"prefix":"10.1111","volume":"62","author":[{"given":"Mie","family":"Kurosawa","sequence":"first","affiliation":[{"name":"Division of Microbiology and Infectious Diseases Graduate School of Medical and Dental Sciences Niigata University 2\u20105274 Gakkocho\u2010dori Chuo\u2010ku Niigata 951\u20108514 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