{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:30:57Z","timestamp":1790141457786,"version":"4.0.1"},"reference-count":58,"publisher":"American Chemical Society (ACS)","issue":"2","license":[{"start":{"date-parts":[[2017,12,29]],"date-time":"2017-12-29T00:00:00Z","timestamp":1514505600000},"content-version":"vor","delay-in-days":1176,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Background: Nephrotoxicity associated with lead poisoning has been frequently reported in epidemiological studies, but the underlying mechanisms have not been fully described.<\/jats:p>\n                  <jats:p>Objectives: We examined the role of erythrocytes, one of the major lead reservoirs, in lead-associated nephrotoxicity.<\/jats:p>\n                  <jats:p>Methods and results: Co-incubation of lead-exposed human erythrocytes with HK-2 human renal proximal tubular cells resulted in renal tubular cytotoxicity, suggesting a role of erythrocytes in lead-induced nephrotoxicity. Morphological and flow cytometric analyses revealed that HK-2 cells actively phagocytized lead-exposed erythrocytes, which was associated with phosphatidylserine (PS) externalization on the erythrocyte membrane and generation of PS-bearing microvesicles. Increased oxidative stress and up-regulation of nephrotoxic biomarkers, such as NGAL, were observed in HK-2 cells undergoing erythrophagocytosis. Moreover, TGF-\u03b2, a marker of fibrosis, was also significantly up-regulated. We examined the significance of erythrophagocytosis in lead-induced nephrotoxicity in rats exposed to lead via drinking water for 12 weeks. We observed iron deposition and generation of oxidative stress in renal tissues of lead-exposed rats, as well as the histopathological alterations such as tubulointerstitial lesions, fibrosis, and up-regulation of KIM-1, NGAL, and TGF-\u03b2.<\/jats:p>\n                  <jats:p>Conclusions: Our data strongly suggest that erythrophagocytosis and subsequent iron deposition in renal tubular cells could significantly enhance nephrotoxicity following lead exposure, providing insight on lead-associated kidney damages.<\/jats:p>\n                  <jats:p>Citation: Kwon SY, Bae ON, Noh JY, Kim K, Kang S, Shin YJ, Lim KM, Chung JH. 2015. Erythrophagocytosis of lead-exposed erythrocytes by renal tubular cells: possible role in lead-induced nephrotoxicity. Environ Health Perspect 123:120\u2013127;\u2002http:\/\/dx.doi.org\/10.1289\/ehp.1408094<\/jats:p>","DOI":"10.1289\/ehp.1408094","type":"journal-article","created":{"date-parts":[[2014,10,10]],"date-time":"2014-10-10T12:04:56Z","timestamp":1412942696000},"page":"120-127","source":"Crossref","is-referenced-by-count":41,"title":["Erythrophagocytosis of Lead-Exposed Erythrocytes by Renal Tubular Cells: Possible Role in Lead-Induced Nephrotoxicity"],"prefix":"10.1021","volume":"123","author":[{"given":"So-Youn","family":"Kwon","sequence":"first","affiliation":[{"name":"College of Pharmacy, Seoul National University, Seoul, Korea"},{"name":"These authors contributed equally to this research."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ok-Nam","family":"Bae","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Hanyang University, Ansan, Korea"},{"name":"These authors contributed equally to this research."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Yoon","family":"Noh","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Seoul National University, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keunyoung","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Seoul National University, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seojin","family":"Kang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Seoul National University, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Jun","family":"Shin","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Hanyang University, Ansan, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung-Min","family":"Lim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Ewha Womans University, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Ho","family":"Chung","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Seoul National University, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2014,10,10]]},"reference":[{"key":"2026080605025118400_micit1","unstructured":"ATSDR (Agency for Toxic Substances and Disease Registry).\n          \n          2007. 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