Neutrophil-specific reduction in the expression of granulocyte--macrophage colony-stimulating factor receptor subunits in myelodysplastic syndromes.
The proliferative and differentiative response of neutrophils to granulocyte-macrophage colony-stimulating factor (GM-CSF) is known to be impaired in patients with myelodysplastic syndromes (MDS). To investigate the mechanisms of the defective response in MDS, we examined expression levels of GM-CSF receptor alpha (GMR alpha) and common beta (beta c) subunits on CD16(+) neutrophils, CD14(+) monocytes and CD3(+) T cells from 26 MDS patients and 10 healthy controls using flow cytometry. Expression of GMR alpha was significantly decreased on the neutrophils of five out of 26 patients and was not specific for any FAB subtype. In contrast, beta c expression on neutrophils was significantly reduced in 14 out of 26 patients with a higher proportion occurring in the advanced stages of MDS including refractory anaemia with excess of blasts (RAEB), RAEB in transformation (RAEBt) and overt leukaemia compared with refractory anaemia (RA)/RA with ringed sideroblasts (RARS) or healthy controls. Decreased beta c also correlated with the degree of hypogranular neutrophil morphology and increased infection. Expression of both subunits on T cells and monocytes in MDS was similar to normal controls. Polymerase chain reaction amplification of reverse-transcribed mRNA isolated from the affected neutrophils suggests that the reduction of beta c may result from decreased message levels. The observed reduction in GM-CSF receptor expression could account for the impaired proliferative and maturational responses in MDS.
Shikama
Y
Y
Division of Blood Transfusion and Transplantation Immunology, First Department of Internal Medicine, Fukushima Medical University, Fukushima, Japan.
Shichishima
T
T
Ohto
H
H
Jubinsky
P T
PT
Maruyama
Y
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000753:Anemia, Refractory / Q000378:metabolism; D000754:Anemia, Refractory, with Excess of Blasts / Q000378:metabolism; D000756:Anemia, Sideroblastic / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology; D016022:Case-Control Studies; D002454:Cell Differentiation; D002455:Cell Division; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007938:Leukemia / Q000378:metabolism; D015477:Leukemia, Myelomonocytic, Chronic / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D017452:Receptors, IgG / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D017252:CD3 Complex; D018950:Lipopolysaccharide Receptors; D020033:Protein Isoforms; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D017452:Receptors, IgG