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  1. Article ; Online: Disruption of Cxcr3 chemotactic signaling alters lysosomal function and renders macrophages more microbicidal

    Frida Sommer / Vincenzo Torraca / Yufei Xie / Aliede E. in ‘t Veld / Joost Willemse / Annemarie H. Meijer

    Cell Reports, Vol 35, Iss 2, Pp 109000- (2021)

    2021  

    Abstract: Summary: Chemotaxis and lysosomal function are closely intertwined processes essential for the inflammatory response and clearance of intracellular bacteria. We used the zebrafish model to examine the link between chemotactic signaling and lysosome ... ...

    Abstract Summary: Chemotaxis and lysosomal function are closely intertwined processes essential for the inflammatory response and clearance of intracellular bacteria. We used the zebrafish model to examine the link between chemotactic signaling and lysosome physiology in macrophages during mycobacterial infection and wound-induced inflammation in vivo. Macrophages from zebrafish larvae carrying a mutation in a chemokine receptor of the Cxcr3 family display upregulated expression of vesicle trafficking and lysosomal genes and possess enlarged lysosomes that enhance intracellular bacterial clearance. This increased microbicidal capacity is phenocopied by inhibiting the lysosomal transcription factor EC, while its overexpression counteracts the protective effect of chemokine receptor mutation. Tracking macrophage migration in zebrafish revealed that lysosomes of chemokine receptor mutants accumulate in the front half of cells, preventing macrophage polarization during chemotaxis and reaching sites of inflammation. Our work shows that chemotactic signaling affects the bactericidal properties and localization during chemotaxis, key aspects of the inflammatory response.
    Keywords macrophage ; chemotaxis ; lysosome ; vesicle ; zebrafish ; mycobacteria ; Biology (General) ; QH301-705.5
    Subject code 572
    Language English
    Publishing date 2021-04-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Immunomonitoring of Tacrolimus in Healthy Volunteers

    Aliede E. in ‘t Veld / Hendrika W. Grievink / Mahdi Saghari / Frederik E. Stuurman / Marieke L. de Kam / Aiko P. J. de Vries / Brenda C. M. de Winter / Jacobus Burggraaf / Adam F. Cohen / Matthijs Moerland

    International Journal of Molecular Sciences, Vol 20, Iss 19, p

    The First Step from PK- to PD-Based Therapeutic Drug Monitoring?

    2019  Volume 4710

    Abstract: Therapeutic drug monitoring is routinely performed to maintain optimal tacrolimus concentrations in kidney transplant recipients. Nonetheless, toxicity and rejection still occur within an acceptable concentration-range. To have a better understanding of ... ...

    Abstract Therapeutic drug monitoring is routinely performed to maintain optimal tacrolimus concentrations in kidney transplant recipients. Nonetheless, toxicity and rejection still occur within an acceptable concentration-range. To have a better understanding of the relationship between tacrolimus dose, tacrolimus concentration, and its effect on the target cell, we developed functional immune tests for the quantification of the tacrolimus effect. Twelve healthy volunteers received a single dose of tacrolimus, after which intracellular and whole blood tacrolimus concentrations were measured and were related to T cell functionality. A significant correlation was found between tacrolimus concentrations in T cells and whole blood concentrations (r = 0.71, p = 0.009), while no correlation was found between tacrolimus concentrations in peripheral blood mononuclear cells (PBMCs) and whole blood (r = 0.35, p = 0.27). Phytohemagglutinin (PHA) induced the production of IL-2 and IFNγ, as well as the inhibition of CD71 and CD154 expression on T cells at 1.5 h post-dose, when maximum tacrolimus levels were observed. Moreover, the in vitro tacrolimus effect of the mentioned markers corresponded with the ex vivo effect after dosing. In conclusion, our results showed that intracellular tacrolimus concentrations mimic whole blood concentrations, and that PHA-induced cytokine production (IL-2 and IFNγ) and activation marker expression (CD71 and CD154) are suitable readout measures to measure the immunosuppressive effect of tacrolimus on the T cell.
    Keywords immunosuppressive drugs ; transplantation ; pharmacodynamics ; pharmacokinetics ; tacrolimus ; therapeutic drug monitoring ; immunomonitoring ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2019-09-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

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