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
- Issue Date
- Feb-2015
- Publisher
- US Department of Health and Human Services
- Citation
- Environmental Health Perspectives, v.123, no.2, pp.120 - 127
- Indexed
- SCIE
SCOPUS
- Journal Title
- Environmental Health Perspectives
- Volume
- 123
- Number
- 2
- Start Page
- 120
- End Page
- 127
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/18870
- DOI
- 10.1289/ehp.1408094
- ISSN
- 0091-6765
- 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.
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