Acid isoferritin inhibitory activity.

The paper by Lu et al.’ appearing recently in Blood adds to the already considerable contributions made by this group supporting the hypothesis that acidic isoferritins play an important regulating role for hemopoietic progenitor cells in vitro. While the evidence in favor of this hypothesis has now become substantial, a number of inconsistencies remain and the term “acidic isoferritin” has never been clearly defined in this context. The acidic isoferritins found in nonhemopoietic tissues, such as heart or HeLa cells, contain a high proportion of H subunits, react to an antibody raised against heart or HeLa ferritin, and do not bind to concanavalin-A. Similar isoferritins occur in most hemopoietic cells, including lymphocytes, monocytes, neutrophil polymorphs, erythrocytes, and erythroblasts.2 In addition to these, acidic isoferritins, again defined by their isoelectric point, occur in plasma, but these do not normally react with an antibody to heart or HeLa ferritin; they contain a glycosylated subunit, and bind to concanavalin-A-Sepharose.5 They can be converted to more basic isoferritins by treatment with neuraminidase. The properties described for the leukaemia-associated inhibitory activity (LIA), which appears to have been identified as an isoferritin, are a composite of characteristics of different isoferritins and do not correspond to any species characterized up to now. If, as Lu et al. suggest, the acidic isoferritin inhibitory activity derives only from normal bone marrow and blood cells of the mononuclear phagocytic lineage, then we have to explain how these specific isoferritins differ from the apparently similar molecules produced by other hemopoietic cells. It is particularly intriguing to speculate on the mode of action of acidic isoferritins on erythroid progenitor cells when recent studies indicate that erythroblasts may contain between 10 and 100 fg ofacidic ferritin per cell.