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Published on: April 3, 2017
Inclusion bodies of aggregated hemosiderins in liver macrophages
Hisao Hayashi1, Yasuaki Tatsumi2, Shinya Wakusawa3
1Department of Medicine, Aichi Gakuin University School of Pharmacy, Nagoya, Japan. hhayashi@dpc.agu.ac.jp.
Abstract:
Hemosiderin formation is a structural indication of iron overload. We investigated further adaptations of the liver to excess iron. Five patients with livers showing iron-rich inclusions larger than 2 µm were selected from our database. The clinical features of patients and structures of the inclusions were compared with those of 2 controls with mild iron overload. All patients had severe iron overload with more than 5000 ng/mL of serum ferritin. Etiologies were variable, from hemochromatosis to iatrogenic iron overload. Their histological stages were either portal fibrosis or cirrhosis. Inclusion bodies were ultra-structurally visualized as aggregated hemosiderins in the periportal macrophages. X-ray analysis always identified, in addition to a large amount of iron complexes including oxygen and phosphorus, a small amount of copper and sulfur in the mosaic matrixes of inclusions. There were no inclusions in the control livers. Inclusion bodies, when the liver is loaded with excess iron, may appear in the macrophages as isolated organella of aggregated hemosiderins. Trace amounts of copper-sulfur complexes were always identified in the mosaic matrices of the inclusions, suggesting cuproprotein induction against excess iron. In conclusion, inclusion formation in macrophages may be an adaptation of the liver loaded with excess iron.
Insights
Liver macrophages form inclusion bodies containing aggregated hemosiderin and trace copper-sulfur complexes in response to severe iron overload. This may represent a protective adaptation to excess iron, observed in patients with conditions like hemochromatosis.
Area of Science:
- Hepatology
- Cellular Biology
- Pathology
Background:
- Hemosiderin formation signifies iron overload.
- The liver's adaptive responses to excess iron require further investigation.
- Understanding these adaptations is crucial for managing iron overload disorders.
Purpose of the Study:
- To investigate the structural and compositional adaptations of the liver in response to severe iron overload.
- To characterize the nature of iron-rich inclusions found in macrophages within overloaded livers.
- To explore potential mechanisms underlying these cellular adaptations.
Main Methods:
- Selection of five patients with severe iron overload and large iron-rich inclusions (>2 µm) in liver biopsies.
- Comparison of patient liver histology and inclusion structures with two control subjects.
- Ultrastructural visualization of inclusions and X-ray analysis for elemental composition.
Main Results:
- Patients presented with severe iron overload (serum ferritin >5000 ng/mL) and advanced fibrosis or cirrhosis.
- Inclusions were identified as aggregated hemosiderins within periportal macrophages.
- X-ray analysis revealed iron, oxygen, phosphorus, and trace amounts of copper and sulfur within the inclusion matrix.
Conclusions:
- Inclusion body formation in macrophages appears to be an adaptive response to severe hepatic iron overload.
- The presence of copper-sulfur complexes suggests a potential role for cuproprotein induction.
- These findings offer insights into cellular mechanisms for managing iron toxicity in the liver.
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