Altered surface expression of effector cell molecules on neutrophils in myelodysplastic syndromes

Abstract

Summary. 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 ¼ 7) and high clinical risk (H-MDS, n ¼ 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.

Flow cytometric method for enumeration and classification of reactive immature granulocyte populations

“…However, results from tests on blood samples from patients with CML, MDS, and from patients treated with G-CSF showed that there is a limitation for this flow cytometric method. Abnormal expression of CD16 or CD11b has been known to exist in certain disorders: a decreased expression of CD16 and elevated expression of CD11b has been observed in the mature neutrophils from patients with MDS (11,12,23). Our own data showed a flow cytometric IG (CD16 -neutrophils) count significantly higher than by manual microscopy (flow cytometry 25.5% versus manual IG 10.0%).…”

Infections in myelodysplastic syndromes

“…[40][41][42] MDS patients also have deficiencies in the contents of neutrophil granules, including quantitative and/or functional anomalies of myeloperoxidase, lactoferrin and antibiotic proteases such as elastase and cathepsin G, [43][44][45][46] deficiencies in granule membrane glycoproteins, 44 and matrix metalloproteinase dysfunction. [47][48][49] Impaired activity of granule proteases in neutrophils, which can induce tissue injury through an inflammatory-mediated process, is potentially implicated in the increased susceptibility to infections even in the absence of neutropenia.…”

Pyoderma Gangrenosum Following Cytosine Arabinoside, Aclarubicin and Granulocyte Colony-Stimulating Factor Combination Therapy in Myelodysplastic Syndrome.

“…However, while the O2~-releasing capacity of neutrophils from some patients is markedly depressed, it is increased in others (5). In addition, we showed that neutrophils from high clinical risk MDSpatients exhibited a higherexpression of CD1 lb/CD 1 8 and a lower expression ofLselectin, indicating an in vivo activation of MDSneutrophils (6). It has been reported that neutrophils from a MDSpatient, who was associated with Sweet's syndrome, exhibited increased O2~-releasing capacity (7).…”

“…The cause of PGremains obscure. Neutrophil functions, such as superoxide (O2~) release and expression of cellular adhesion molecules, are impaired in some MDSpatients (5,6). However, while the O2~-releasing capacity of neutrophils from some patients is markedly depressed, it is increased in others (5).…”