@article{Roel P. Gazendam_Annemarie van de Geer_John L. van Hamme_Anton T.J. Tool_Dieke J. van Rees_Cathelijn E.M. Aarts_Maartje van den Biggelaar_Floris van Alphen_Paul Verkuijlen_Alexander B. Meijer_Hans Janssen_Dirk Roos_Timo K. van den Berg_Taco W. Kuijpers_2016, place={Pavia, Italy}, title={Impaired killing of Candida albicans by granulocytes mobilized for transfusion purposes: a role for granule components}, volume={101}, url={https://haematologica.org/article/view/7707}, DOI={10.3324/haematol.2015.136630}, abstractNote={Granulocyte transfusions are used to treat neutropenic patients with life-threatening bacterial or fungal infections that do not respond to anti-microbial drugs. Donor neutrophils that have been mobilized with granulocyte-colony stimulating factor (G-CSF) and dexamethasone are functional in terms of antibacterial activity, but less is known about their fungal killing capacity. We investigated the neutrophil-mediated cytotoxic response against <em>C. albicans</em> and <em>A. fumigatus</em> in detail. Whereas G-CSF/dexamethasone-mobilized neutrophils appeared less mature as compared to neutrophils from untreated controls, these cells exhibited normal ROS production by the NADPH oxidase system and an unaltered granule mobilization capacity upon stimulation. G-CSF/dexamethasone-mobilized neutrophils efficiently inhibited <em>A. fumigatus</em> germination and killed <em>Aspergillus</em> and <em>Candida</em> hyphae, but the killing of <em>C. albicans</em> yeasts was distinctly impaired. Following normal <em>Candida</em> phagocytosis, analysis by mass spectrometry of purified phagosomes after fusion with granules demonstrated that major constituents of the antimicrobial granule components, including major basic protein (MBP), were reduced. Purified MBP showed candidacidal activity, and neutrophil-like Crisp-Cas9 NB4-KO-MBP differentiated into phagocytes were impaired in <em>Candida</em> killing. Together, these findings indicate that G-CSF/dexamethasone-mobilized neutrophils for transfusion purposes have a selectively impaired capacity to kill <em>Candida</em&gt; yeasts, as a consequence of an altered neutrophil granular content.}, number={5}, journal={Haematologica}, author={Roel P. Gazendam and Annemarie van de Geer and John L. van Hamme and Anton T.J. Tool and Dieke J. van Rees and Cathelijn E.M. Aarts and Maartje van den Biggelaar and Floris van Alphen and Paul Verkuijlen and Alexander B. Meijer and Hans Janssen and Dirk Roos and Timo K. van den Berg and Taco W. Kuijpers}, year={2016}, month={Apr.}, pages={587-596} }