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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-YounBae, Ok-NamNoh, Ji-YoonKim, KeunyoungKang, SeojinShin, Young-JunLim, Kyung-MinChung, Jin-Ho
Ewha Authors
임경민
SCOPUS Author ID
임경민scopus
Issue Date
2015
Journal Title
ENVIRONMENTAL HEALTH PERSPECTIVES
ISSN
0091-6765JCR Link1552-9924JCR Link
Citation
vol. 123, no. 2, pp. 120 - 127
Publisher
US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
Indexed
SCI; SCIE; SCOPUS WOS
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
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약학대학 > 약학과 > Journal papers
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