{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T10:48:06Z","timestamp":1761216486098},"reference-count":0,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2000,1,1]],"date-time":"2000-01-01T00:00:00Z","timestamp":946684800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 GM62112"],"award-info":[{"award-number":["R01 GM62112"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Mediators of Inflammation"],"published-print":{"date-parts":[[2002,1]]},"abstract":"<jats:p><jats:italic>Background<\/jats:italic>: Calprotectin is a calcium\u2010binding and zinc\u2010binding protein complex that is abundant in the cytosol of neutrophils. This factor is composed of 8 and 14 kDa subunits, which have also been termed migration inhibitory factor\u2010related proteins MRP8 and MRP14. We previously reported that rat calprotectin purified from inflammatory neutrophils induces apoptosis of various tumor cells or normal fibroblasts in a zinc\u2010reversible manner.<\/jats:p><jats:p><jats:italic>Aim<\/jats:italic>: The present study was undertaken to elucidate which subunit is responsible for the apoptosis\u2010inducing activity, and to explore the mechanism of zinc\u2010reversible apoptosis induction.<\/jats:p><jats:p><jats:italic>Methods<\/jats:italic>: The apoptosis\u2010inducing activity of recombinant human MRP8 (rhMRP8) and recombinant human MRP14 (rhMRP14) was examined against EL\u20104 lymphoma cells <jats:italic>in vitro<\/jats:italic>. To determine whether zinc deprivation by calprotectin was essential for the cytotoxicity, the activity of calprotectin was tested under conditions where physical contact between the factor and the cells was precluded by a low molecular weight cut\u2010off dialysis membrane.<\/jats:p><jats:p><jats:italic>Results<\/jats:italic>: The cytotoxicity of rhMRP14 against EL\u20104 cells was first detected at 10 \u03bcM in a standard medium, whereas rhMRP8 caused only marginal cytotoxicity at 40 \u03bcM. A mixture of both proteins showed higher specific activity (onset of cytotoxicity at 5 \u03bcM). When the cells were cultured in divalent cation\u2010depleted medium, each dose\u2010response curve was shifted to about a four\u2010fold lower concentration range. Calprotectin was found to induce cell death even when the complex and the target cells were separated by dialysis membrane. A membrane\u2010impermeable zinc chelator, diethylenetriamine pentaacetic acid (DTPA), also induced target cell apoptosis in a similar time\u2010course as calprotectin. Moreover, the activities of calprotectin and DTPA were completely inhibited by the presence of zinc ions.<\/jats:p><jats:p><jats:italic>Conclusion<\/jats:italic>: These data indicate that calprotectin has higher specific activity to induce apoptosis than the individual subunits, and that the mechanism is exclusion of zinc from target cells.<\/jats:p>","DOI":"10.1080\/09622935020138208","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:37:56Z","timestamp":1027701476000},"page":"165-172","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Implication of extracellular zinc exclusion by recombinant human calprotectin (MRP8 and MRP14) from target cells in its apoptosis\u2010inducing activity"],"prefix":"10.1155","volume":"11","author":[{"given":"Satoru","family":"Yui","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuichi","family":"Nakatani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Hunter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Walter J.","family":"Chazin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masatoshi","family":"Yamazaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2002,1]]},"container-title":["Mediators of Inflammation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/mi\/2002\/187569.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1080\/09622935020138208","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T23:57:31Z","timestamp":1723075051000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1080\/09622935020138208"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,1]]},"references-count":0,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2002,1]]}},"alternative-id":["10.1080\/09622935020138208"],"URL":"https:\/\/doi.org\/10.1080\/09622935020138208","archive":["Portico"],"relation":{},"ISSN":["0962-9351","1466-1861"],"issn-type":[{"type":"print","value":"0962-9351"},{"type":"electronic","value":"1466-1861"}],"subject":[],"published":{"date-parts":[[2002,1]]},"assertion":[{"value":"2002-01-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}