Eine Plattform für die Wissenschaft: Bauingenieurwesen, Architektur und Urbanistik
Eine Plattform für die Wissenschaft: Bauingenieurwesen, Architektur und Urbanistik
Neutrophil biology in chronic lymphocytic leukaemia and infections
Bacterial infections are the leading cause of morbidity and mortality in patients suffering from Chronic Lymphocytic Leukaemia (CLL). CLL is characterised by accumulation of malignant B-cells in the peripheral blood and neutrophils are crucial to fight off infections. However, the contribution of neutrophils during the antibacterial response in CLL has not been elucidated. This study has employed a murine adoptive transfer model by intravenously injecting splenocytes from Eμ-TCL1 transgenic mice into syngeneic wildtype mice. We found CLL B-cells in lymphoid as well as non-lymphoid organs, such as the urinary bladder and the lung. Proteome and flow cytometric analysis of neutrophils from CLL mice showed a rather mature and activated phenotype through enhanced frequencies of CD11b+, CXCR2+ and ICAM1+ and decreased frequencies of CXCR4+ and CD62L+.Such aberrant neutrophil phenotype coincided with a severe urinary tract infection (UTI) after inoculating uropathogenic E.coli (UPEC). Also in this murine infection model, neutrophils showed an activated and functionally altered neutrophil phenotype in CLL. The phenotype of neutrophils showed enhanced TGF-bRI, CD62L, cKit and CXCR4 frequencies and was immunosuppressed and immature at the site of infection. Moreover, the phagocytic function of neutrophils was diminished during CLL and MPO levels declined in neutrophils of CLL mice. Additionally, neutrophil numbers during UTI inversely correlated with bacterial burden in CLL indicating a recruitment defect. However, migratory defects in neutrophils from CLL were not found in a 3D-in vitro migration assay. Finally, phenotypical characterization of neutrophils from untreated CLL patients confirmed the murine findings by showing decreased frequencies of CD10+, CXCR4+ and CD62L+ and increased frequencies of ICAM1+ and PDL1+.In conclusion, this study provides comprehensive evidence on the functional alterations in the phenotype of neutrophils as well as modulation of the antibacterial response by neutrophils in CLL. Restoration ...
Neutrophil biology in chronic lymphocytic leukaemia and infections
Bacterial infections are the leading cause of morbidity and mortality in patients suffering from Chronic Lymphocytic Leukaemia (CLL). CLL is characterised by accumulation of malignant B-cells in the peripheral blood and neutrophils are crucial to fight off infections. However, the contribution of neutrophils during the antibacterial response in CLL has not been elucidated. This study has employed a murine adoptive transfer model by intravenously injecting splenocytes from Eμ-TCL1 transgenic mice into syngeneic wildtype mice. We found CLL B-cells in lymphoid as well as non-lymphoid organs, such as the urinary bladder and the lung. Proteome and flow cytometric analysis of neutrophils from CLL mice showed a rather mature and activated phenotype through enhanced frequencies of CD11b+, CXCR2+ and ICAM1+ and decreased frequencies of CXCR4+ and CD62L+.Such aberrant neutrophil phenotype coincided with a severe urinary tract infection (UTI) after inoculating uropathogenic E.coli (UPEC). Also in this murine infection model, neutrophils showed an activated and functionally altered neutrophil phenotype in CLL. The phenotype of neutrophils showed enhanced TGF-bRI, CD62L, cKit and CXCR4 frequencies and was immunosuppressed and immature at the site of infection. Moreover, the phagocytic function of neutrophils was diminished during CLL and MPO levels declined in neutrophils of CLL mice. Additionally, neutrophil numbers during UTI inversely correlated with bacterial burden in CLL indicating a recruitment defect. However, migratory defects in neutrophils from CLL were not found in a 3D-in vitro migration assay. Finally, phenotypical characterization of neutrophils from untreated CLL patients confirmed the murine findings by showing decreased frequencies of CD10+, CXCR4+ and CD62L+ and increased frequencies of ICAM1+ and PDL1+.In conclusion, this study provides comprehensive evidence on the functional alterations in the phenotype of neutrophils as well as modulation of the antibacterial response by neutrophils in CLL. Restoration ...
Neutrophil biology in chronic lymphocytic leukaemia and infections
Vijitha, Nirojah (Autor:in) / Engel, Daniel Robert
21.04.2021
Hochschulschrift
Elektronische Ressource
Englisch
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