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Altered surface expression of effector cell molecules on neutrophils in myelodysplastic syndromes
1Department of Internal Medicine, Hitachi General Hospital, Ibaraki, Japan.
Abstract:
The surface expression of effector cell molecules on neutrophils was examined in 18 patients with myelodysplastic syndromes (MDS) and 20 healthy control subjects. The MDS patients were further classified as low clinical risk (L-MDS, n=7) and high clinical risk (H-MDS, n=11). The expression of Fc receptors for IgG (FcR), complement receptors (CR) and cellular adhesion molecules on neutrophils was determined by flow cytometry and monoclonal antibodies. The effect of granulocyte colony-stimulating factor (G-CSF) and tumour necrosis factor-alpha (TNF) on L-selectin shedding and CR up-regulation on neutrophils was also examined. The percentage of FcRI-positive neutrophils and CD11b/CR3 expression on neutrophils were significantly increased in the H-MDS patients when compared to the controls. In contrast, the expression of FcRII, FcRIII, L-selectin, LFA-1 and CD18 on neutrophils was significantly reduced in the H-MDS patients compared with the controls. The L-MDS neutrophils exhibited lower expressions of CR1, L-selectin, LFA-1 and CD18 than those of the controls. Neutrophils from some H-MDS patients showed impaired L-selectin shedding and CR up-regulation after stimulation with G-CSF or TNF, although these were not significantly different when assessed in the whole H-MDS group. These findings suggest that an altered surface expression of effector cell molecules and an impaired modulation of cellular adhesion molecules on neutrophils may contribute to the increased susceptibility to bacterial infections in MDS patients.
Insights
Myelodysplastic syndromes (MDS) alter neutrophil surface molecules, increasing infection risk. High-risk MDS patients show abnormal Fc receptor and adhesion molecule expression, impacting immune response.
Area of Science:
- Immunology
- Hematology
- Cell Biology
Background:
- Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic stem cell disorders.
- MDS patients exhibit increased susceptibility to infections, particularly bacterial infections.
- Neutrophils play a critical role in innate immunity and host defense against bacterial pathogens.
Purpose of the Study:
- To investigate the surface expression of effector cell molecules on neutrophils in patients with myelodysplastic syndromes (MDS).
- To compare neutrophils from low-risk (L-MDS) and high-risk (H-MDS) MDS patients with healthy controls.
- To assess the impact of G-CSF and TNF on neutrophil function in MDS.
Main Methods:
- Flow cytometry and monoclonal antibodies were used to determine the expression of Fc receptors (FcR), complement receptors (CR), and cellular adhesion molecules on neutrophils.
- Neutrophils from 18 MDS patients (7 L-MDS, 11 H-MDS) and 20 healthy controls were analyzed.
- The effect of G-CSF and TNF on L-selectin shedding and CR up-regulation was examined.
Main Results:
- H-MDS patients showed significantly increased FcRI and CD11b/CR3 expression on neutrophils compared to controls.
- Reduced expression of FcRII, FcRIII, L-selectin, LFA-1, and CD18 was observed on neutrophils from H-MDS patients.
- L-MDS neutrophils exhibited lower expression of CR1, L-selectin, LFA-1, and CD18 than controls.
- Some H-MDS patients displayed impaired L-selectin shedding and CR up-regulation upon G-CSF or TNF stimulation.
Conclusions:
- Altered surface expression of effector cell molecules on neutrophils is a characteristic feature of MDS.
- Impaired modulation of cellular adhesion molecules on neutrophils may contribute to the increased susceptibility to bacterial infections in MDS patients.
- These findings highlight potential therapeutic targets for improving immune function in MDS.