The distribution of iron and iron binding proteins in spleen with reference to Hodgkin's disease

Abstract

Summary The distribution of iron and iron binding proteins (IBP) Hodgkin's disease (HD) is a progressive disorder of' the lymphoid system often accompanied by a deficiency in cell mediated immunity (Hansen & Good, 1974;Kaplan, 1976). The depression of cell mediated immunity in HD has been related to increased activity of suppressor cells (Twomey et al., 1980;Hillinger & Herzig, 1978;Goodwin et al., 1977; Sibbett et al., 1978), the presence of circulating inhibitory factors (Siegal, 1976; Fuks et al., 1976;Moroz et al., 1977), and, in advanced disease, decreased numbers of T-cells, (Aiuti et al., 1973;Bukowski et al., 1976). De Sousa et al. (1977 have reported poor proliferative responses to phytohaemaglutinin (PHA) of peripheral blood lymphocytes from patients with HD when compared with normal controls, corrected by splenectomy. This data coupled with observations of increased T-cell percentages in the spleens from patients with HD (Kaur et al., 1974;Payne et al., 1976;Gupta, 1980) led De Sousa et al. (1977 to postulate that depressed cell immunity in the blood is a consequence of the sequestration of a particular T-cell subset in the spleen and further to suggest that this may be associated with the presence of iron binding proteins (IBP) in the cells of the reticuloendothelial system (De Sousa et al., 1978 Anomalies of iron handling by the phagocytic system in HD were first described by Beamish et al. (1972). De Sousa et al. (1977 examined iron deposition and the distribution of IBP in five spleens involved with the disease and one nonHodgkin's lymphoma control. IBP were identified by immunofluorescent staining of frozen sections and iron by Perls Prussian blue technique. These results claimed a relationship between the distribution in the spleen of iron and IBP and involvement with HD. Smithyman et al. (1979) confirmed that elevated levels of ferritin were found in frozen sections of HD spleens, but again the study was small and the frozen section technique employed gave poor morphological detail. These reports suggest a specific relationship between IBP and, or, iron and the development of a cellular defect in HD. We were doubtful that this was so and this scepticism prompted us to study the distribution of iron and IBP not only in HD but also in other disorders including non-Hodgkin's lymphomas, thalassaemia and carcinoma where the haematological changes associated with HD may not occur.We present the results of a study of splenic tissue from 63 cases of lymphoma, 49 of which were from patients with HD. Various non-lymphomatous control spleens were included in the study incorporating spleens from patients with thalassaemia, a disease with a known abnormality in iron metabolism.

Magnetic mapping of iron in rodent spleen

“…Iron is primarily located in the ferritin core present in the cytoplasm and in the lysosomes present in macrophages in the red pulp. 39–41 Although we did not specifically stain for macrophages or ferritin using IHC, iron could be easily localized using Perl’s staining of sections from OCT embedded tissue. Electron dense regions and EDS analysis confirmed the presence of iron in TEM images.…”

Local iron homeostasis in the breast ductal carcinoma microenvironment

“…Several studies had already focused on the establishment of associations between the immune profile of the infiltrating leukocytes in the tumor and established clinicopathological variables of breast cancer outcome [ 44 – 46 ] but very few have approached the association with iron-related proteins. Interestingly, Britten et al had already demonstrated that spleens from patients with Hodgink’s disease presented a higher expression of ferritin in macrophages, particularly around tumor nodules [ 47 ]. The present results point to the fact that deregulation of iron metabolism occurs not only at the primary tumor microenvironment, but also in preferential metastatic niches.…”

Iron overload secondary to cirrhosis: a mimic of hereditary haemochromatosis?

“…However, this is not unexpected, given the spleen's role in the reticuloendothelial system. Stainable iron can be present in the normal spleen, and might be predicted to increase in the setting of cirrhosis, which is sometimes accompanied by low‐grade haemolysis . Despite this, in the majority of cases splenic iron was modest.…”