ABSTRACT
Congenital dyserythropoietic anaemia type II (CDA II) is well known for glycosylation abnormalities affecting erythrocyte membrane glycoconjugates that encompass hypoglycosylation of band 3 glycoprotein and accumulation of glycosphingolipids: lactotriaosylceramides, neolactotriaosylceramide and polyglycosylceramides. These abnormalities were not observed in erythrocytes from patients with CDA of either type I or III. Recently, however, we have described a CDA type I patient in Poland with identical, though less pronounced, glycoconjugate abnormalities to those observed in patients with CDA type II. The abnormalities included partial unglycosylation of O-linked glycosylation sites in glycophorin A. These abnormalities are now reported in three Bedouin patients from Israel with CDA type I. In addition, the erythrocyte membranes of these patients exhibited highly increased globotetraosylceramide content. Glycoconjugate abnormalities were also present in erythrocyte membranes from three patients from Northern Sweden with CDA type III but they almost exclusively affected glycosphingolipids. In erythrocytes of all patients examined including one with CDA type II, polyglycosylceramides were significantly hypoglycosylated although, on a molar basis, their contents in erythrocyte membranes were increased. Thus, glycoconjugate abnormalities of varying intensity occur in erythrocyte membranes from all patients with CDA that were investigated.
Subject(s)
Anemia, Dyserythropoietic, Congenital/blood , Erythrocyte Membrane/metabolism , Glycoconjugates/metabolism , Anemia, Dyserythropoietic, Congenital/classification , Anion Exchange Protein 1, Erythrocyte/chemistry , Anion Exchange Protein 1, Erythrocyte/metabolism , Case-Control Studies , Glycoconjugates/chemistry , Glycophorins/chemistry , Glycophorins/metabolism , Glycosylation , HumansABSTRACT
Leukemic leukocytes from 12 patients with acute myelogenous leukemia (AML) and two patients with chronic myelogenous leukemia (CML) were isolated by centrifugations in Percoll gradients, and examined for total carbohydrates. In leukemic leukocytes from 10 of these patients ceramide-bound carbohydrates were also determined. Protein-bound carbohydrates were calculated by subtraction of ceramide-bound carbohydrates from total carbohydrates. In all samples analysed the contents of total and protein-bound carbohydrates were much lower in leukemic leukocytes than in normal neutrophils, irrespective whether the results were expressed relative to protein, DNA, cell number or dry mass. For immature leukemic cells of M0-M1 phenotype differences up to 10-fold were observed. Contents of ceramide-bound carbohydrates, i.e. those of neutral and acidic glycosphingolipids (GSLs) were also low in leukemic cells. However, when GSL carbohydrates were calculated as percentage of total carbohydrates, GSLs in leukemic leukocytes were elevated in half of the AML patients but depressed in the other half. The results are discussed in the light of the hypothesis on GSL function by one of us (Koscielak J., 1986, Glycoconjugate J. 3, 95-108). According to one element of the hypothesis, during cell differentiation newly synthesized glycoproteins (GPs) that perform specific functions are added to house-keeping GPs that are present in plasma membranes of all types of cells. Thus, during differentiation, the GP content of the cell membrane should increase and that of the so called "membrane packing" glycosphingolipids should decrease.
Subject(s)
Carbohydrate Metabolism , Leukemia, Myeloid, Acute/blood , Leukocytes/metabolism , Carbohydrates/chemistry , Cell Transformation, Neoplastic , Humans , Leukemia, Myeloid, Acute/pathology , Leukocytes/pathology , Protein Binding , ProteinsABSTRACT
The kinetics of interferon production, induced by poly I:C in the presence of DEAE dextran, was studied in Lpa cells. Optimal interferon production was obtained at concentration of 10 micrograms/ml poly I:C and 200 micrograms/ml DEAE dextran. Transfer RNA applied to Lpa cells during induction and synthesis of interferon resulted in continuous production of interferon for 24 hrs. The application of tRNA to cells during the shutoff of interferon synthesis had no effect on the kinetics of interferon production.