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.
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.
Authors: Santosh L Saraf; Xu Zhang; Binal Shah; Tamir Kanias; Krishnamurthy P Gudehithlu; Rick Kittles; Roberto F Machado; Jose A L Arruda; Mark T Gladwin; Ashok K Singh; Victor R Gordeuk Journal: Haematologica Date: 2015-07-23 Impact factor: 9.941
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