In vitro erythrophagocytosis by renal tubular cells and tubular toxicity by haemoglobin and iron

Neil S. Sheerin, Steven H. Sacks, Giovanni B. Fogazzi

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Background. Patients with gross haematuria of glomerular origin may develop acute tubular necrosis and reversible renal failure. Erythrocytes within the cytoplasm of proximal tubular epithelial cells (PTECs) can be seen on examination of renal biopsies from these patients. It is possible, therefore, that the tubular damage is a result of cytotoxic breakdown products released during erythrocyte degradation. Methods. To test this hypothesis, we evaluated (i) by transmission electron microscopy, the capability of a PTEC line to phagocytose and degrade erythrocytes in vitro; and (ii) the effect on the viability of PTCEs in vitro both after erythrophagocytosis and after incubation with haemoglobin, free iron or both. Results. Electron microscopic examination of PTECs exposed to erythrocytes for 96 h showed that 22% of PTECs contained one or more erythrocyte. These were within phagolysosomes and showed varying stages of degradation, with collapse and breakdown of the cell membrane and invasion by cytoplasmic organelles (the so-called haemolytic pathway of erythrocyte degradation). Despite the phagocytosis and degradation of the erythrocytes, no cytotoxicity could be demonstrated under the experimental conditions used. However, the presence of haemoglobin, free iron or both in the culture medium was toxic to the PTECs. resulting in a significant reduction in the number of viable cells present. Conclusions. PTECs are able to phagocytose and degrade erythrocytes, and haemoglobin and iron are toxic to proximal tubular cells in vitro.

Original languageEnglish
Pages (from-to)1391-1397
Number of pages7
JournalNephrology Dialysis Transplantation
Volume14
Issue number6
DOIs
Publication statusPublished - 1999

Fingerprint

Hemoglobins
Iron
Erythrocytes
Kidney
Epithelial Cells
Phagocytosis
Poisons
Phagosomes
In Vitro Techniques
Hematuria
Transmission Electron Microscopy
Organelles
Renal Insufficiency
Culture Media
Cytoplasm
Necrosis
Cell Count
Cell Membrane
Electrons
Biopsy

Keywords

  • Acute tubular necrosis
  • Erythrocyte degradation
  • Erythrophagocytosis
  • Haemoglobin tubular toxicity
  • Iron tubular toxicity
  • Proximal tubular cell culture

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

In vitro erythrophagocytosis by renal tubular cells and tubular toxicity by haemoglobin and iron. / Sheerin, Neil S.; Sacks, Steven H.; Fogazzi, Giovanni B.

In: Nephrology Dialysis Transplantation, Vol. 14, No. 6, 1999, p. 1391-1397.

Research output: Contribution to journalArticle

Sheerin, Neil S. ; Sacks, Steven H. ; Fogazzi, Giovanni B. / In vitro erythrophagocytosis by renal tubular cells and tubular toxicity by haemoglobin and iron. In: Nephrology Dialysis Transplantation. 1999 ; Vol. 14, No. 6. pp. 1391-1397.
@article{6fde4a9c062f4fe78fe79935abe37e3e,
title = "In vitro erythrophagocytosis by renal tubular cells and tubular toxicity by haemoglobin and iron",
abstract = "Background. Patients with gross haematuria of glomerular origin may develop acute tubular necrosis and reversible renal failure. Erythrocytes within the cytoplasm of proximal tubular epithelial cells (PTECs) can be seen on examination of renal biopsies from these patients. It is possible, therefore, that the tubular damage is a result of cytotoxic breakdown products released during erythrocyte degradation. Methods. To test this hypothesis, we evaluated (i) by transmission electron microscopy, the capability of a PTEC line to phagocytose and degrade erythrocytes in vitro; and (ii) the effect on the viability of PTCEs in vitro both after erythrophagocytosis and after incubation with haemoglobin, free iron or both. Results. Electron microscopic examination of PTECs exposed to erythrocytes for 96 h showed that 22{\%} of PTECs contained one or more erythrocyte. These were within phagolysosomes and showed varying stages of degradation, with collapse and breakdown of the cell membrane and invasion by cytoplasmic organelles (the so-called haemolytic pathway of erythrocyte degradation). Despite the phagocytosis and degradation of the erythrocytes, no cytotoxicity could be demonstrated under the experimental conditions used. However, the presence of haemoglobin, free iron or both in the culture medium was toxic to the PTECs. resulting in a significant reduction in the number of viable cells present. Conclusions. PTECs are able to phagocytose and degrade erythrocytes, and haemoglobin and iron are toxic to proximal tubular cells in vitro.",
keywords = "Acute tubular necrosis, Erythrocyte degradation, Erythrophagocytosis, Haemoglobin tubular toxicity, Iron tubular toxicity, Proximal tubular cell culture",
author = "Sheerin, {Neil S.} and Sacks, {Steven H.} and Fogazzi, {Giovanni B.}",
year = "1999",
doi = "10.1093/ndt/14.6.1391",
language = "English",
volume = "14",
pages = "1391--1397",
journal = "Nephrology Dialysis Transplantation",
issn = "0931-0509",
publisher = "Oxford University Press",
number = "6",

}

TY - JOUR

T1 - In vitro erythrophagocytosis by renal tubular cells and tubular toxicity by haemoglobin and iron

AU - Sheerin, Neil S.

AU - Sacks, Steven H.

AU - Fogazzi, Giovanni B.

PY - 1999

Y1 - 1999

N2 - Background. Patients with gross haematuria of glomerular origin may develop acute tubular necrosis and reversible renal failure. Erythrocytes within the cytoplasm of proximal tubular epithelial cells (PTECs) can be seen on examination of renal biopsies from these patients. It is possible, therefore, that the tubular damage is a result of cytotoxic breakdown products released during erythrocyte degradation. Methods. To test this hypothesis, we evaluated (i) by transmission electron microscopy, the capability of a PTEC line to phagocytose and degrade erythrocytes in vitro; and (ii) the effect on the viability of PTCEs in vitro both after erythrophagocytosis and after incubation with haemoglobin, free iron or both. Results. Electron microscopic examination of PTECs exposed to erythrocytes for 96 h showed that 22% of PTECs contained one or more erythrocyte. These were within phagolysosomes and showed varying stages of degradation, with collapse and breakdown of the cell membrane and invasion by cytoplasmic organelles (the so-called haemolytic pathway of erythrocyte degradation). Despite the phagocytosis and degradation of the erythrocytes, no cytotoxicity could be demonstrated under the experimental conditions used. However, the presence of haemoglobin, free iron or both in the culture medium was toxic to the PTECs. resulting in a significant reduction in the number of viable cells present. Conclusions. PTECs are able to phagocytose and degrade erythrocytes, and haemoglobin and iron are toxic to proximal tubular cells in vitro.

AB - Background. Patients with gross haematuria of glomerular origin may develop acute tubular necrosis and reversible renal failure. Erythrocytes within the cytoplasm of proximal tubular epithelial cells (PTECs) can be seen on examination of renal biopsies from these patients. It is possible, therefore, that the tubular damage is a result of cytotoxic breakdown products released during erythrocyte degradation. Methods. To test this hypothesis, we evaluated (i) by transmission electron microscopy, the capability of a PTEC line to phagocytose and degrade erythrocytes in vitro; and (ii) the effect on the viability of PTCEs in vitro both after erythrophagocytosis and after incubation with haemoglobin, free iron or both. Results. Electron microscopic examination of PTECs exposed to erythrocytes for 96 h showed that 22% of PTECs contained one or more erythrocyte. These were within phagolysosomes and showed varying stages of degradation, with collapse and breakdown of the cell membrane and invasion by cytoplasmic organelles (the so-called haemolytic pathway of erythrocyte degradation). Despite the phagocytosis and degradation of the erythrocytes, no cytotoxicity could be demonstrated under the experimental conditions used. However, the presence of haemoglobin, free iron or both in the culture medium was toxic to the PTECs. resulting in a significant reduction in the number of viable cells present. Conclusions. PTECs are able to phagocytose and degrade erythrocytes, and haemoglobin and iron are toxic to proximal tubular cells in vitro.

KW - Acute tubular necrosis

KW - Erythrocyte degradation

KW - Erythrophagocytosis

KW - Haemoglobin tubular toxicity

KW - Iron tubular toxicity

KW - Proximal tubular cell culture

UR - http://www.scopus.com/inward/record.url?scp=0033011569&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033011569&partnerID=8YFLogxK

U2 - 10.1093/ndt/14.6.1391

DO - 10.1093/ndt/14.6.1391

M3 - Article

VL - 14

SP - 1391

EP - 1397

JO - Nephrology Dialysis Transplantation

JF - Nephrology Dialysis Transplantation

SN - 0931-0509

IS - 6

ER -