Human Isoferritins: Organ Specific Iron and Apoferritin Distribution

Abstract

Ferritins from human liver, spleen, heart, pancreas and kidney were compared by electrophoresis and isoelectric focusing in polyacrylamide gels, by immunodiffusion against antisera to homologous and heterologous ferritin, and in some cases by their cyanogen bromide peptides. All ferritins appeared to consist of a single species on gel electrophoresis with the exception of heart ferritin which separated into two major components. Small differences in electrophoretic mobility were found in all tissue ferritins. By contrast, all tissue ferritins were found to consist of multiple forms when analysed by gel electrofocusing. At least five isoferritins were found in most tissues, several of which were common to most tissues. At least two were common to all tissues. Those ferritins which were most easily distinguishable electrophoretically, e.g. spleen and heart ferritin, showed the greatest differences on gel electrofocusing. The ferritin profile was characteristic of each organ and was reproducible both within individuals and between individual tissues. There were striking differences in the iron content of the various isoferritins within a tissue. Further, the iron content of isoferritins common to more than one tissue varied with the tissue of origin. Some isoferritins in several organs and all of the isoferritins in pancreas appeared to contain little, if any, iron. All five tissue ferritins contained antigenic determinants in common with liver ferritin. However, an additional antigenic determinant was found in liver ferritin which was not detectable in the ferritins from the other organs.

Isoferritins in acute leukaemia

“…With immunodiffusion methods, rabbit antisera to human spleen ferritin appear to recognize any normal human isoferritin, so that the detection of ferritin by immunoprecipitation after IEF is unlikely to be affected by such differing immunoreactivities. Similar findings have been reported with antisera to liver ferritin (Arosio et al, 1976;Powell et al, 1975a). After density-gradient centrifugation the concentration of more acidic ferritins would also be underestimated.…”

“…However, acidic isoferritins are also widely distributed in normal tissues such as heart, kidney, pancreas (Powell et at., 1975a), placenta (Drysdale and Singer, 1974) and reticulocytes (Worwood et al, 1976a). Normal liver and spleen seem to be exceptional in not normally possessing the more acidic proteins.…”

“…On isoelectric focusing, ferritin is seen to consist of a number of " isoferritins ", some of which are common to all tissues (Powell et al, 1975a). The more acidic isoferritins are found in heart and kidney (Powell et al, 1975a), in placenta (Drysdale and Singer, 1974) and foetal tissues (Alpert, Coston and Drysdale, 1973), in hepatoma (Alpert et al, 1973), in carcinoma of the breast and pancreas (Marcus and Zinberg, 1974) and in HeLa cells (Drysdale and Singer, 1974).…”

“…The more acidic isoferritins are found in heart and kidney (Powell et al, 1975a), in placenta (Drysdale and Singer, 1974) and foetal tissues (Alpert, Coston and Drysdale, 1973), in hepatoma (Alpert et al, 1973), in carcinoma of the breast and pancreas (Marcus and Zinberg, 1974) and in HeLa cells (Drysdale and Singer, 1974). Such acidic isoferritins, when appearing in tissues which do not normally contain them, such as liver, have been called " carcinofoetal " ferritin (Alpert et al, 1973).…”

Serum ferritin concentration in early breast cancer

“…Elevated levels have been reported in leukaemia and Hodgkin's disease (Jones et al, 1973) and, in the case of acute leukaemia, this is associated with increased synthesis and high concentrations in the malignant cells White et al, 1974). The analysis of normal tissue ferritin by isoelectric focusing has revealed considerable heterogeneity (Drysdale, 1974;Powell et al, 1975). Alpert, Coston and Drysdale (1973) found human hepatoma tissue to contain an acidic ferritin also present in early foetal liver but not in mature liver.…”