Abstract
The distribution of ferritin antigenicity in control and iron-loaded rat hepatocytes was investigated with an immunogold-ferritin antibody technique. Antibody to horse spleen ferritin showed immunoreactivity as determined by dot blotting with immunogold/silver staining with purified rat liver ferritin but not with rat haemosiderin. The initial site of ferritin degradation was studied by analysing the density of gold labelling in the cytosol and lysosomes in combination with pre-embedding acid phosphatase cytochemistry. Immunoreactive ferritin was present in the cytosol, cytosolic clusters and lysosomes of normal hepatocytes. After iron-loading, the labelling density increased over tenfold in parenchymal cell cytosol with a smaller increase in Kupffer cells. Ferritin clusters contained substantially more immunoreactive ferritin than equivalent areas of lysosomes or cytosol. Analysis of the labelling density in hepatocyte lysosomes showed that, despite a striking increase in iron content, one-quarter of the lysosomes showed less immunolabelled ferritin than the cytosol. The existence of a wide range of ferritin labelling densities in the lysosomes with a large proportion unlabelled suggests that the ferritin protein shell is not degraded at a significant rate either in the cytosol or in clusters but only after incorporation into lysosomes.
MeSH Terms
Acid Phosphatase/analysis
Animals
Cytosol/analysis,enzymology,ultrastructure
Ferritins/analysis,immunology,metabolism
Immunohistochemistry/methods
Liver/analysis,cytology,enzymology
Lysosomes/analysis,enzymology,ultrastructure
Male
Microscopy, Electron/methods
Rats
Rats, Inbred Strains
Chemicals
Ferritins
Acid Phosphatase
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Cooper P J
Division of Clinical Cell Biology, MRC Clinical Research Centre, Harrow, Middlesex, UK.
Iancu T C
Ward R J
Guttridge K M
Peters T J
References (21)
21 references, click to expand
-
The relevance of various tests for the study of specificity in immunocytochemical staining: a review.
Cell Biochem Funct. 1986 Jan;4(1):1-17
PMID: 2417739
-
Ascorbic acid inhibits lysosomal autophagy of ferritin.
J Biol Chem. 1987 Oct 25;262(30):14773-8
PMID: 3667602
-
Pathogenetic mechanisms in hepatic cirrhosis of thalassemia major: light and electron microscopic studies.
Pathol Annu. 1977;12 Pt 1:171-200
PMID: 917591
-
Enhancement of structural preservation and immunocytochemical staining in low temperature embedded pancreatic tissue.
J Histochem Cytochem. 1981 May;29(5):663-71
PMID: 6166664
-
Ultrastructural observations in the carbonyl iron-fed rat, an animal model for hemochromatosis.
Virchows Arch B Cell Pathol Incl Mol Pathol. 1987;53(4):208-17
PMID: 2890233
-
Sensitive visualization of antigen-antibody reactions in dot and blot immune overlay assays with immunogold and immunogold/silver staining.
J Immunol Methods. 1984 Nov 30;74(2):353-60
PMID: 6209340
-
Cytochemical contributions to differentiating GERL from the Golgi apparatus.
Histochem J. 1977 Sep;9(5):525-51
PMID: 198392
-
The efficiency of immunolabel on Lowicryl sections compared to theoretical predictions.
J Histochem Cytochem. 1987 Sep;35(9):959-69
PMID: 3302020
-
Perfusion and immersion fixation of rat liver with glutaraldehyde.
Lab Invest. 1967 May;16(5):736-50
PMID: 5338187
-
A procedure for the purification of ferritin from human liver by heating a methanol-treated homogenate.
Anal Biochem. 1985 Dec;151(2):561-5
PMID: 4096386
-
Antibodies to the Golgi complex and the rough endoplasmic reticulum.
J Cell Biol. 1982 Jan;92(1):92-107
PMID: 7199056
-
Biliary excretion of iron from hepatocyte lysosomes in the rat. A major excretory pathway in experimental iron overload.
J Clin Invest. 1986 Jan;77(1):90-7
PMID: 3944262
-
Cytochemical demonstration of phosphatases in the rat liver by a cerium-based method in combination with osmium tetroxide and potassium ferrocyanide postfixation.
Histochemistry. 1983;78(1):71-9
PMID: 6307935
-
Haemosiderin-like properties of free-radical-modified ferritin.
Biochem J. 1986 Nov 15;240(1):297-300
PMID: 3827850
-
Iron overload.
Mol Aspects Med. 1983;6(1):1-100
PMID: 6371428
-
Biochemical studies on the isolation and characterization of human spleen haemosiderin.
Biochem J. 1984 Oct 1;223(1):31-8
PMID: 6497844
-
On the structure of hemosiderin and its relationship to ferritin.
J Ultrastruct Res. 1971 Dec;37(5):495-503
PMID: 5136270
-
Studies of iron overload. Lysosomal proteolysis of rat liver ferritin.
Pathol Res Pract. 1986 May;181(2):159-67
PMID: 3737472
-
Hepatic lipid peroxidation in vivo in rats with chronic iron overload.
J Clin Invest. 1983 Mar;71(3):429-39
PMID: 6826715
-
Studies of iron overload. Rat liver siderosome ferritin.
Lab Invest. 1984 Jan;50(1):26-35
PMID: 6694350
-
The iron-loaded cell--the cytopathology of iron storage. A review.
Am J Pathol. 1978 May;91(2):362-404
PMID: 347943