دورية أكاديمية

Humanized MISTRG as a preclinical in vivo model to study human neutrophil-mediated immune processes.

التفاصيل البيبلوغرافية
العنوان: Humanized MISTRG as a preclinical in vivo model to study human neutrophil-mediated immune processes.
المؤلفون: Martinez-Sanz P; Sanquin Research and Landsteiner Laboratory, Department of Molecular Hematology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands., Laurent ARG; Sanquin Research and Landsteiner Laboratory, Department of Hematopoiesis, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands., Slot E; Sanquin Research and Landsteiner Laboratory, Department of Hematopoiesis, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands., Hoogenboezem M; Sanquin Research and Landsteiner Laboratory, Department of Molecular Hematology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands., Bąbała N; Sanquin Research and Landsteiner Laboratory, Department of Hematopoiesis, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands., van Bruggen R; Sanquin Research and Landsteiner Laboratory, Department of Molecular Hematology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands., Rongvaux A; Department of Immunology, University of Washington, Seattle, WA, United States.; Fred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA, United States., Flavell RA; Department of Immunobiology, Yale University School of Medicine, New Haven, CT, United States.; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT, United States., Tytgat GAM; Princess Maxima Center for Pediatric Oncology, Department of Pediatric Oncology, Utrecht, Netherlands., Franke K; Sanquin Research and Landsteiner Laboratory, Department of Molecular Hematology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands., Matlung HL; Sanquin Research and Landsteiner Laboratory, Department of Molecular Hematology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands., Kuijpers TW; Sanquin Research and Landsteiner Laboratory, Department of Hematopoiesis, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.; Rheumatology and Infectious Diseases, Emma Children's Hospital, Department of Pediatric Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands., Amsen D; Sanquin Research and Landsteiner Laboratory, Department of Hematopoiesis, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands., Karrich JJ; Sanquin Research and Landsteiner Laboratory, Department of Hematopoiesis, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
المصدر: Frontiers in immunology [Front Immunol] 2023 Mar 08; Vol. 14, pp. 1105103. Date of Electronic Publication: 2023 Mar 08 (Print Publication: 2023).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Lausanne : Frontiers Research Foundation]
مواضيع طبية MeSH: Neutrophils* , Heterocyclic Compounds*, Humans ; Mice ; Animals ; Hematopoietic Stem Cell Mobilization ; Bone Marrow ; Immunity
مستخلص: Introduction: MISTRG mice have been genetically modified to allow development of a human myeloid compartment from engrafted human CD34+ haemopoietic stem cells, making them particularly suited to study the human innate immune system in vivo . Here, we characterized the human neutrophil population in these mice to establish a model that can be used to study the biology and contribution in immune processes of these cells in vivo .
Methods and Results: We could isolate human bone marrow neutrophils from humanized MISTRG mice and confirmed that all neutrophil maturation stages from promyelocytes (CD11b-CD16-) to end-stage segmented cells (CD11b+CD16+) were present. We documented that these cells possessed normal functional properties, including degranulation, reactive oxygen species production, adhesion, and antibody-dependent cellular cytotoxicity towards antibody-opsonized tumor cells ex vivo . The acquisition of functional capacities positively correlated with the maturation state of the cell. We found that human neutrophils were retained in the bone marrow of humanized MISTRG mice during steady state. However, the mature segmented CD11b+CD16+ human neutrophils were released from the bone marrow in response to two well-established neutrophil-mobilizing agents (i.e., G-CSF and/or CXCR4 antagonist Plerixafor). Moreover, the neutrophil population in the humanized MISTRG mice actively reacted to thioglycolate-induced peritonitis and could infiltrate implanted human tumors, as shown by flow cytometry and fluorescent microscopy.
Discussion: These results show that functional human neutrophils are generated and can be studied in vivo using the humanized MISTRG mice, providing a model to study the various functions of neutrophils in inflammation and in tumors.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 Martinez-Sanz, Laurent, Slot, Hoogenboezem, Bąbała, van Bruggen, Rongvaux, Flavell, Tytgat, Franke, Matlung, Kuijpers, Amsen and Karrich.)
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فهرسة مساهمة: Keywords: MISTRG; animal model; humanized immune system mouse; neutrophils; next generation humanized mouse models; preclinical study
المشرفين على المادة: 0 (Heterocyclic Compounds)
تواريخ الأحداث: Date Created: 20230327 Date Completed: 20230328 Latest Revision: 20230328
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC10032520
DOI: 10.3389/fimmu.2023.1105103
PMID: 36969261
قاعدة البيانات: MEDLINE