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Article ; Online: Neutrophils in sickle cell disease: Exploring their potential role as a therapeutic target.

de Ligt, Lydian A / Gaartman, Aafke E / Biemond, Bart J / Fijnvandraat, Karin / van Bruggen, Robin / Nur, Erfan

2024 Volume 99, Issue 6, Page(s) 1119–1128

Abstract: Factors influencing the activation of neutrophils in SCD and the potential neutrophil-mediated ameliorating effects of therapies in SCD. ...

Abstract	Factors influencing the activation of neutrophils in SCD and the potential neutrophil-mediated ameliorating effects of therapies in SCD.
MeSH term(s)	Anemia, Sickle Cell/therapy ; Anemia, Sickle Cell/drug therapy ; Humans ; Neutrophils/pathology ; Neutrophil Activation/drug effects
Language	English
Publishing date	2024-01-31
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	196767-8
ISSN	1096-8652 ; 0361-8609
ISSN (online)	1096-8652
ISSN	0361-8609
DOI	10.1002/ajh.27224
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Zs.A 1251: Show issues

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Article ; Online: Cultured CD71

Alshalani, Abdulrahman / Beuger, Boukje M / van Bruggen, Robin / Acker, Jason P / Juffermans, Nicole P

Transfusion medicine (Oxford, England)

2023 Volume 33, Issue 3, Page(s) 257–262

Abstract: Objective: The study aimed to determine the impact of Red Blood Cells (RBCs) generated from peripheral blood mononuclear cells (PBMCs) on T cell proliferation and host response following whole blood stimulation.: Background: Culturing RBCs is a ... ...

Abstract	Objective: The study aimed to determine the impact of Red Blood Cells (RBCs) generated from peripheral blood mononuclear cells (PBMCs) on T cell proliferation and host response following whole blood stimulation. Background: Culturing RBCs is a potential solution for donor shortage. The impact of immature cultured RBCs which express CD71 Methods/materials: PBMCs were seeded in an erythroid expansion medium. CD71 Results: At day 9, the percentage of cells that expressed CD45 and CD71 reached to the highest level (32.9%, IQR; 26.2-39.05) while the percentage of cells that expressed CD71 and CD235a reached to the highest level on day 17 (70.2%, IQR; 66.1-72.8). Incubation of T cells with days 14 CD71 Conclusion: Cultured erythroid cells can modulate the immune response by promoting T cell proliferation and inhibiting cytokine secretions following whole blood stimulation.
MeSH term(s)	Humans ; Cells, Cultured ; Erythrocytes ; Erythroid Cells ; Immunity ; Leukocytes, Mononuclear
Chemical Substances	CD71 antigen
Language	English
Publishing date	2023-03-15
Publishing country	England
Document type	Journal Article
ZDB-ID	1067989-3
ISSN	1365-3148 ; 0958-7578
ISSN (online)	1365-3148
ISSN	0958-7578
DOI	10.1111/tme.12964
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Zs.A 3177: Show issues

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Article ; Online: Novel concepts in red blood cell clearance.

Neri, Silvia / Swinkels, Dorine W / Matlung, Hanke L / van Bruggen, Robin

Current opinion in hematology

2021 Volume 28, Issue 6, Page(s) 438–444

Abstract: Purpose of review: Red blood cell (RBC) clearance has been studied for decades in many different pathologies, which has revealed different routes of RBC degradation, depending on the situation. This review summarizes the latest mechanistic insights on ... ...

Abstract	Purpose of review: Red blood cell (RBC) clearance has been studied for decades in many different pathologies, which has revealed different routes of RBC degradation, depending on the situation. This review summarizes the latest mechanistic insights on RBC clearance in different contexts; during homeostatic removal, immune-mediated destruction, and systemic inflammation. Recent findings: Besides the recognition of a variety of potential 'eat me' signals on RBCs, recent evidence suggests that normal RBC degradation is driven by the increase of the adhesive properties of RBCs, mediating the retention in the spleen and leading to RBC hemolysis. Furthermore, immune-mediated degradation of RBCs seems to be fine-tuned by the balance between the density of the antigens expressed on RBCs and the presence of 'don't eat me' signals. Moreover, besides RBC clearance by macrophages, neutrophils seem to play a much more prominent role in immune-mediated RBC removal than anticipated. Lastly, RBC clearance during systemic inflammation appears to be driven by a combination of extreme macrophage activity in response to proinflammatory cytokines as well as direct damage of RBC by the inflammation or inflammatory agent. Summary: Recent studies on RBC clearance have expanded our knowledge on their destruction in different contexts.
MeSH term(s)	Erythrocytes/cytology ; Hemolysis ; Humans ; Inflammation/blood ; Macrophages/cytology ; Neutrophils/cytology
Language	English
Publishing date	2021-09-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1153887-9
ISSN	1531-7048 ; 1065-6251
ISSN (online)	1531-7048
ISSN	1065-6251
DOI	10.1097/MOH.0000000000000679
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Article ; Online: Efficient complement-mediated clearance of immunosuppressed T cells by macrophages.

Gankema, Angela A F / Furumaya, Charita / Fernández-Hermira, Sara / Hoogenboezem, Mark / Matlung, Hanke L / van Bruggen, Robin / Kuijpers, Taco W

Frontiers in immunology

2023 Volume 14, Page(s) 1183180

Abstract: Cancer is one of the leading causes of death worldwide. Treatment outcome is largely dictated by the tumor type, disease stage, and treatment success rates, but also by the variation among patients in endogenous anti-tumor responses. Studies indicate ... ...

Abstract	Cancer is one of the leading causes of death worldwide. Treatment outcome is largely dictated by the tumor type, disease stage, and treatment success rates, but also by the variation among patients in endogenous anti-tumor responses. Studies indicate that the presence of neutrophils in the tumor microenvironment is associated with a worse patient outcome due to their ability to suppress local anti-tumor T cell activity. Our previous studies investigated the mechanisms by which neutrophils suppress and damage T cells to become smaller in size (small T cells), debilitating their effector activities. Several studies indicate a role for tumor-associated macrophages in scavenging damaged or dead cells. We hypothesized that the observed lack of small T cells in the TME by confocal microscopy is due to immediate uptake by macrophages. In this study, we confirmed that indeed only the smaller, damaged T cells are taken up by macrophages, once serum-opsonized. Damaged T cells opsonized with complement factor C3 fragments were phagocytosed by macrophages, resulting in almost instantaneous and highly efficient uptake of these small T cells. Inhibition of the complement receptors CR1, CR3 and CR4 expressed by macrophages completely blocked phagocytosis. By contrast, actively proliferating T cells (large T cells) were neither impaired in neutrophil-MDSC activity nor opsonized for phagocytosis by macrophages. Rapid removal of damaged T cells suggests a role of complement and macrophages within the tumor microenvironment to clear suppressed T cells in cancer patients.
MeSH term(s)	Humans ; Receptors, Complement 3b ; T-Lymphocytes ; Macrophages ; Receptors, Complement/physiology ; Complement C3
Chemical Substances	Receptors, Complement 3b ; Receptors, Complement ; Complement C3
Language	English
Publishing date	2023-05-16
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1183180
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Article: The impact of biological age of red blood cell on

Alshalani, Abdulrahman / Beuger, Boukje M / Tuip-de Boer, Anita M / van Bruggen, Robin / Acker, Jason P / Juffermans, Nicole P

Frontiers in physiology

2023 Volume 14, Page(s) 1127103

Abstract: Introduction: ...

Abstract	Introduction:
Language	English
Publishing date	2023-03-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2023.1127103
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Article ; Online: Lack of eosinophil extracellular trap formation due to failure of plasma membrane breakdown in the absence of elastase.

Sprenkeler, Evelien G G / Goetschalckx, Ines / Fernández Hermira, Sara / Tool, Anton T J / Hoogenboezem, Mark / van Bruggen, Robin / Kuijpers, Taco W

Blood advances

2023 Volume 7, Issue 19, Page(s) 5868–5876

Abstract: Activated eosinophils are described to release eosinophil extracellular traps (EETs), which consist of the cell's DNA covered with granule-derived antimicrobial peptides. Upon stimulation of eosinophils with the known EET-inducers phorbol 12-myristate 13- ...

Abstract	Activated eosinophils are described to release eosinophil extracellular traps (EETs), which consist of the cell's DNA covered with granule-derived antimicrobial peptides. Upon stimulation of eosinophils with the known EET-inducers phorbol 12-myristate 13-acetate, monosodium urate crystals, or Candida albicans, we observed that their plasma membrane became compromised, resulting in accessibility of the nuclear DNA for staining with the impermeable DNA dye Sytox Green. However, we did not observe any DNA decondensation or plasma membrane rupture by eosinophils, which sharply contrasts with neutrophil extracellular trap (NET) formation and the subsequent cell death known as NETosis. Neutrophil elastase (NE) activity is thought to be essential for the cleavage of histones and chromatin decondensation during NETosis. We observed that the neutrophils of a patient with a mutation in ELANE, leading to congenital neutropenia and NE deficiency, were unable to undergo NETosis. Taken together, we may suggest that the natural absence of any NE-like proteolytic activity in human eosinophils explains why EET formation is not observed, even when eosinophils become positive for an impermeable DNA dye in response to stimuli that induce NETosis in neutrophils.
MeSH term(s)	Humans ; Extracellular Traps/metabolism ; Neutrophils/metabolism ; Histones/metabolism ; DNA/metabolism ; Cell Membrane/metabolism
Chemical Substances	Histones ; DNA (9007-49-2)
Language	English
Publishing date	2023-07-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2022009432
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Zs.A 7153: Show issues

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Article ; Online: Reduced myeloid commitment and increased uptake by macrophages of stem cell-derived HPS2 neutrophils.

Webbers, Steven Ds / Aarts, Cathelijn Em / Klein, Bart / Koops, Dané / Geissler, Judy / Tool, Anton Tj / van Bruggen, Robin / van den Akker, Emile / Kuijpers, Taco W

Life science alliance

2024 Volume 7, Issue 4

Abstract: Hermansky-Pudlak syndrome type 2 (HPS2) is a rare autosomal recessive disorder, caused by mutations in ... ...

Abstract	Hermansky-Pudlak syndrome type 2 (HPS2) is a rare autosomal recessive disorder, caused by mutations in the
MeSH term(s)	Animals ; Humans ; Hermanski-Pudlak Syndrome/genetics ; Hermanski-Pudlak Syndrome/metabolism ; Neutrophils/metabolism ; Mutation ; Macrophages/metabolism
Language	English
Publishing date	2024-01-18
Publishing country	United States
Document type	Journal Article
ISSN	2575-1077
ISSN (online)	2575-1077
DOI	10.26508/lsa.202302263
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Article ; Online: SKAP2 acts downstream of CD11b/CD18 and regulates neutrophil effector function.

Bouti, Panagiota / Klein, Bart J A M / Verkuijlen, Paul J H / Schornagel, Karin / van Alphen, Floris P J / Taris, Kees-Karel H / van den Biggelaar, Maartje / Hoogendijk, Arie J / van Bruggen, Robin / Kuijpers, Taco W / Matlung, Hanke L

Frontiers in immunology

2024 Volume 15, Page(s) 1344761

Abstract: Background: The importance of CD11b/CD18 expression in neutrophil effector functions is well known. Beyond KINDLIN3 and TALIN1, which are involved in the induction of the high-affinity binding CD11b/CD18 conformation, the signaling pathways that ... ...

Abstract	Background: The importance of CD11b/CD18 expression in neutrophil effector functions is well known. Beyond KINDLIN3 and TALIN1, which are involved in the induction of the high-affinity binding CD11b/CD18 conformation, the signaling pathways that orchestrate this response remain incompletely understood. Method: We performed an unbiased screening method for protein selection by biotin identification (BioID) and investigated the KINDLIN3 interactome. We used liquid chromatography with tandem mass spectrometry as a powerful analytical tool. Generation of NB4 CD18, KINDLIN3, or SKAP2 knockout neutrophils was achieved using CRISPR-Cas9 technology, and the cells were examined for their effector function using flow cytometry, live cell imaging, microscopy, adhesion, or antibody-dependent cellular cytotoxicity (ADCC). Results: Among the 325 proteins significantly enriched, we identified Src kinase-associated phosphoprotein 2 (SKAP2), a protein involved in actin polymerization and integrin-mediated outside-in signaling. CD18 immunoprecipitation in primary or NB4 neutrophils demonstrated the presence of SKAP2 in the CD11b/CD18 complex at a steady state. Under this condition, adhesion to plastic, ICAM-1, or fibronectin was observed in the absence of SKAP2, which could be abrogated by blocking the actin rearrangements with latrunculin B. Upon stimulation of NB4 SKAP2-deficient neutrophils, adhesion to fibronectin was enhanced whereas CD18 clustering was strongly reduced. This response corresponded with significantly impaired CD11b/CD18-dependent NADPH oxidase activity, phagocytosis, and cytotoxicity against tumor cells. Conclusion: Our results suggest that SKAP2 has a dual role. It may restrict CD11b/CD18-mediated adhesion only under resting conditions, but its major contribution lies in the regulation of dynamic CD11b/CD18-mediated actin rearrangements and clustering as required for cellular effector functions of human neutrophils.
MeSH term(s)	Humans ; Neutrophils/metabolism ; src-Family Kinases/metabolism ; Fibronectins/metabolism ; CD18 Antigens/metabolism ; Cell Adhesion ; Actins/metabolism ; Phosphoproteins/metabolism ; Macrophage-1 Antigen/metabolism
Chemical Substances	src-Family Kinases (EC 2.7.10.2) ; Fibronectins ; CD18 Antigens ; Actins ; Phosphoproteins ; Macrophage-1 Antigen
Language	English
Publishing date	2024-02-29
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2024.1344761
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Article ; Online: Formation of neutrophil extracellular traps requires actin cytoskeleton rearrangements.

Sprenkeler, Evelien G G / Tool, Anton T J / Henriet, Stefanie S V / van Bruggen, Robin / Kuijpers, Taco W

Blood

2022 Volume 139, Issue 21, Page(s) 3166–3180

Abstract: Neutrophils are important effector cells in the host defense against invading microorganisms. One of the mechanisms they use to eliminate pathogens is the release of neutrophil extracellular traps (NETs). Although NET release and subsequent cell death ... ...

Abstract	Neutrophils are important effector cells in the host defense against invading microorganisms. One of the mechanisms they use to eliminate pathogens is the release of neutrophil extracellular traps (NETs). Although NET release and subsequent cell death known as NETosis have been intensively studied, the cellular components and factors determining or facilitating the formation of NETs remain incompletely understood. Using various actin polymerization and myosin II modulators on neutrophils from healthy individuals, we show that intact F-actin dynamics and myosin II function are essential for NET formation when induced by different stimuli; that is, phorbol 12-myristate 13-acetate, monosodium urate crystals, and Candida albicans. The role of actin polymerization in NET formation could not be explained by the lack of reactive oxygen species production or granule release, which were normal or enhanced under the given conditions. Neutrophils from patients with very rare inherited actin polymerization defects by either actin-related protein 2/3 complex subunit 1B or megakaryoblastic leukemia 1 deficiency also failed to show NETosis. We found that upon inhibition of actin dynamics, there is a lack of translocation of neutrophil elastase to the nucleus, which may explain the impaired NET formation. Collectively, our data show the essential requirement of an intact and active actin polymerization process, as well as active myosin II to enable the release of nuclear DNA by neutrophils during NET formation.
MeSH term(s)	Actin Cytoskeleton ; Actins/metabolism ; Candida albicans ; Extracellular Traps/metabolism ; Humans ; Neutrophils/metabolism
Chemical Substances	Actins
Language	English
Publishing date	2022-01-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2021013565
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Uh III Zs.140: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
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Article: Different MDSC Activity of G-CSF/Dexamethasone Mobilized Neutrophils: Benefits to the Patient?

Aarts, Cathelijn E M / Hiemstra, Ida H / Furumaya, Charita / van Bruggen, Robin / Kuijpers, Taco W

Frontiers in oncology

2020 Volume 10, Page(s) 1110

Abstract: Human neutrophils exert a well-known role as efficient effector cells to kill pathogenic micro-organisms. Apart from their role in innate immunity, neutrophils also have the capacity to suppress T cell-mediated immune responses as so-called granulocyte- ... ...

Abstract	Human neutrophils exert a well-known role as efficient effector cells to kill pathogenic micro-organisms. Apart from their role in innate immunity, neutrophils also have the capacity to suppress T cell-mediated immune responses as so-called granulocyte-myeloid-derived suppressor cells (g-MDSCs), impacting the clinical outcome of various disease settings such as cancer. Patients undergoing chemotherapy because of an underlying malignancy can develop prolonged bone marrow suppression and are prone to serious infections because of severe neutropenia. Concentrates of granulocytes for transfusion (GTX) constitute a therapeutic tool and rescue treatment to fight off these serious bacterial and fungal infections when antimicrobial therapy is ineffective. GTX neutrophils are mobilized by overnight G-CSF and/or Dexamethasone stimulation of healthy donors. Although the phenotype of these mobilized neutrophils differs from the circulating neutrophils under normal conditions, their anti-microbial function is still intact. In contrast to the unaltered antimicrobial effector functions, G-CSF/Dexamethasone-mobilized neutrophils were found to lack suppression of the T cell proliferation, whereas G-CSF-mobilized or Dexamethasone-mobilized neutrophils could still suppress the T cell proliferation upon cell activation equally well as control neutrophils. Although the mechanism of how G-CSF/Dex mobilization may silence the g-MDSC activity of neutrophils without downregulating the antimicrobial activity is presently unclear, their combined use in patients in the treatment of underlying malignancies may be beneficial-irrespective of the number of circulating neutrophils. These findings also indicate that MDSC activity does not fully overlap with the antimicrobial activity of human neutrophils and offers the opportunity to elucidate the feature(s) unique to their T-cell suppressive activity.
Language	English
Publishing date	2020-07-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2020.01110
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