Defective neutrophil function and microbicidal mechanisms in the myelodysplastic disorders.

Martin, Sonja; Baldock, S C; Ghoneim, A T; Child, J. Anthony

doi:10.1136/jcp.36.10.1120

Cited by 75 publications

(24 citation statements)

References 22 publications

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“…No RNA could be isolated from blood at later time points, again related to the virtually complete absence of leukocytes in the circulation. Although defective immune function in leukemic cells has been described before [4,5], we have demonstrated that cytokine production capacity and HLA-DR expression are not affected by DAMP release in leukemia patients treated with chemotherapeutic agents.…”

Section: Resultsmentioning

confidence: 78%

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Release of Danger-Associated Molecular Patterns following Chemotherapy Does Not Induce Immunoparalysis in Leukemia Patients

Timmermans¹,

Leijte²,

Kox³

et al. 2017

Acta Haematol

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Chemotherapy may result in the release of danger-associated molecular patterns (DAMPs), which can cause immunoparalysis (deactivation of the immune system). We investigated DAMPs following chemotherapy and their relationship with markers of immunoparalysis in leukemia patients. In 6 patients with acute myeloid leukemia or myelodysplastic syndrome and 12 healthy subjects, DAMPs, cytokines, and markers of immunoparalysis were determined before and during the first week after chemotherapy initiation. In the patients, plasma levels of nuclear DNA (a marker of general DAMP release) were profoundly increased before chemotherapy and further increased 4-6 h afterwards, while the specific DAMP mitochondrial DNA showed only a trend towards increase. Circulating cytokine levels did not change following chemotherapy. Leukocyte cytokine production capacity and HLA-DR expression were similar in patients and healthy controls until day 4 when leukocytes were found to be virtually absent. In conclusion, in the early phase following chemotherapy in leukemia patients, increased DAMP release does not induce immunoparalysis.

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Section: Resultsmentioning

confidence: 78%

“…It is well-known that chemotherapy-induced immune cell destruction is the major contributor to this decreased immune function [3]. However, defective immune function in remaining cells has also been described, e.g., in neutrophils and T lymphocytes [4,5]. …”

Section: Introductionmentioning

confidence: 99%

Release of Danger-Associated Molecular Patterns following Chemotherapy Does Not Induce Immunoparalysis in Leukemia Patients

Timmermans¹,

Leijte²,

Kox³

et al. 2017

Acta Haematol

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“…MDS neutrophils exhibit a wide spectrum of functional abnormalities, including adhesion, aggregation, chemotaxis, phagocytosis, enzyme content and microbicidal capacity (Boogaerts et al, 1983;Martin et al, 1983;Mazzone et al, 1993). We reported previously that Expression of L-selectin (A) and CR3 (B) on neutrophils in whole blood.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 1997

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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.

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“…2) (12). Excessive production of inflammatory cytokines and abnormal neutrophil functions are frequently observed in MDS (22,23 (25). However, BD-like symptoms are not common in patients with MPDs (26), except for those with chronic myelogenous leukemia treated with interferons (27)(28)(29)(30).…”

Section: Hla-b51 One Of the Common Allele Types Among Japanese Has mentioning

confidence: 99%

Myelodysplastic Syndrome Complicated with Inflammatory Intestinal Ulcers: Significance of Trisomy 8

et al. 2006

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Defective neutrophil function and microbicidal mechanisms in the myelodysplastic disorders.

Cited by 75 publications

References 22 publications

Release of Danger-Associated Molecular Patterns following Chemotherapy Does Not Induce Immunoparalysis in Leukemia Patients

Release of Danger-Associated Molecular Patterns following Chemotherapy Does Not Induce Immunoparalysis in Leukemia Patients

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

Myelodysplastic Syndrome Complicated with Inflammatory Intestinal Ulcers: Significance of Trisomy 8

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