Role of Aberrant Sialylation of Chronic Myeloid Leukemia Granulocytes on Binding and Signal Transduction by Chemotactic Peptides and Colony Stimulating Factors
- 1 January 1993
- journal article
- research article
- Published by Informa UK Limited in Leukemia & Lymphoma
- Vol. 11 (1-2), 79-90
- https://doi.org/10.3109/10428199309054733
Abstract
Chronic myelogenous leukemia (CML) granulocytes exhibit a number of characteristics attributable to immature granulocytes, including marked increases in cell surface sialylation of glycoproteins which may be due, at least in part, to an increased activity of cytidine 5'-monophosphate-N-acetylneuraminic acid:Ga1 beta 1-3Ga1NAc alpha(2-3)-sialyltransferase (EC 2.4.99.4), and perhaps to altered activity of other glycosyltransferases and sialidases. This aberrant sialylation of CML granulocytes contributes to the decreased binding of the synthetic chemotactic peptide, formyl Met Leu Phe (fMLP), to the surface of CML granulocytes which leads to a rapid, transient increase in cytosolic free calcium ([Ca2+]i), an integral step in the biochemical cascade leading to cell activation. To determine if the decrease in binding of fMLP to CML granulocytes translates into a functional deficit, we measured fMLP-induced increases in [Ca2+]i. Compared to normal granulocytes, fMLP-induced increases in [Ca2+]i were markedly decreased in CML granulocytes. After sialidase treatment, a significant augmentation in fMLP-induced increases in [Ca2+]i was noted in CML granulocytes, indicating that the decreased signalling may be a consequence of aberrant sialylation. To determine if the effects of aberrant sialylation also alters the binding of endogenous polypeptide mediators, we determined the effect of desialylation of CML and normal granulocytes on binding of the colony stimulating factor for granulocytes and monocytes (GM-CSF), which plays a role in differentiation and proliferation of myeloid-lineage cells. As with fMLP binding, we also showed that the binding of GM-CSF to CML granulocytes, but not normal granulocytes, was markedly increased after sialidase treatment. Similarly, binding of GM-CSF to undifferentiated HL-60 cells was markedly increased after sialidase treatment. Therefore, we have demonstrated that aberrant sialylation of CML granulocytes not only alters the binding of fMLP and GM-CSF to their receptor(s), but may also alter signal transduction. Thus, aberrant glycosylation of CML granulocytes may reduce the binding of hematopoietic growth factors, which in turn may be responsible for the immature phenotype of CML granulocytes.Keywords
This publication has 21 references indexed in Scilit:
- Structural and functional analyses of glycosylation on the distinct molecules of human GM‐CSF receptorsEuropean Journal of Biochemistry, 1991
- Expression of the GM-CSF gene after retroviral transfer in hematopoietic stem cell lines induces synchronous granulocyte-macrophage differentiationCell, 1991
- Granulocyte/Macrophage Colony Stimulating FactorInternational Archives of Allergy and Immunology, 1989
- Chemotactic factor induced tyrosine phosphorylation of membrane associated proteins in rabbit peritoneal neutrophilsBiochemical and Biophysical Research Communications, 1988
- Transmembrane Ion Fluxes during Activation of Human T Lymphocytes: Role of Ca2+, Na+/H+ Exchange and Phospholipid TurnoverImmunological Reviews, 1987
- Changes in the granulocyte membrane following chemotherapy for chronic myelogenous leukaemiaBritish Journal of Haematology, 1986
- Potential role for a guanine nucleotide regulatory protein in chemoattractant receptor mediated polyphosphoinositide metabolism, Ca++ mobilization and cellular responses by leukocytesBiochemical and Biophysical Research Communications, 1985
- Pertussis toxin inhibits the rise in the intracellular concentration of free calcium that is induced by chemotactic factors in rabbit neutrophils: Possible role of the “G proteins” in calcium mobilizationBiochemical and Biophysical Research Communications, 1984
- Cyclic Nucleotide-induced Maturation of Human Promyelocytic Leukemia CellsJCI Insight, 1982
- Leukokinetic Studies. X. Blood Granulocyte Kinetics in Chronic Myelocytic Leukemia*JCI Insight, 1965