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Erythrophagocytosis of Lead-Exposed Erythrocytes by Renal Tubular Cells: Possible Role in Lead-Induced Nephrotoxicity
- Title
- Erythrophagocytosis of Lead-Exposed Erythrocytes by Renal Tubular Cells: Possible Role in Lead-Induced Nephrotoxicity
- Authors
- Kwon, So-Youn; Bae, Ok-Nam; Noh, Ji-Yoon; Kim, Keunyoung; Kang, Seojin; Shin, Young-Jun; Lim, Kyung-Min; Chung, Jin-Ho
- Ewha Authors
- 임경민
- SCOPUS Author ID
- 임경민

- Issue Date
- 2015
- Journal Title
- ENVIRONMENTAL HEALTH PERSPECTIVES
- ISSN
- 0091-6765
1552-9924
- Citation
- ENVIRONMENTAL HEALTH PERSPECTIVES vol. 123, no. 2, pp. 120 - 127
- Publisher
- US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
- Indexed
- SCI; SCIE; SCOPUS

- Document Type
- Article
- Abstract
- BACKGROUND: Nephrotoxicity associated with lead poisoning has been frequently reported in epidemiological studies, but the underlying mechanisms have not been fully described. OBJECTIVES: We examined the role of erythrocytes, one of the major lead reservoirs, in lead-associated nephrotoxicity. 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-beta, 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-beta. 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.
- DOI
- 10.1289/ehp.1408094
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
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