دورية أكاديمية
Lung Marginated and Splenic Murine Resident Neutrophils Constitute Pioneers in Tissue-Defense During Systemic E. coli Challenge.
| العنوان: | Lung Marginated and Splenic Murine Resident Neutrophils Constitute Pioneers in Tissue-Defense During Systemic E. coli Challenge. |
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| المؤلفون: | Juzenaite G; National Heart and Lung Institute (NHLI), Imperial College London, London, United Kingdom., Secklehner J; National Heart and Lung Institute (NHLI), Imperial College London, London, United Kingdom.; Cancer Research UK Beatson Institute, Glasgow, United Kingdom., Vuononvirta J; National Heart and Lung Institute (NHLI), Imperial College London, London, United Kingdom.; William Harvey Heart Centre, Barts & the London School of Medicine & Dentistry, Queen Mary University of London, London, United Kingdom., Helbawi Y; National Heart and Lung Institute (NHLI), Imperial College London, London, United Kingdom., Mackey JBG; National Heart and Lung Institute (NHLI), Imperial College London, London, United Kingdom.; Cancer Research UK Beatson Institute, Glasgow, United Kingdom., Dean C; National Heart and Lung Institute (NHLI), Imperial College London, London, United Kingdom., Harker JA; National Heart and Lung Institute (NHLI), Imperial College London, London, United Kingdom.; Asthma UK Centre for Allergic Mechanisms of Asthma, London, United Kingdom., Carlin LM; Cancer Research UK Beatson Institute, Glasgow, United Kingdom.; Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom., Rankin S; National Heart and Lung Institute (NHLI), Imperial College London, London, United Kingdom., De Filippo K; National Heart and Lung Institute (NHLI), Imperial College London, London, United Kingdom. |
| المصدر: | Frontiers in immunology [Front Immunol] 2021 Apr 19; Vol. 12, pp. 597595. Date of Electronic Publication: 2021 Apr 19 (Print Publication: 2021). |
| 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: | Cell Movement/*immunology , Escherichia coli/*immunology , Escherichia coli Infections/*immunology , Lung/*immunology , Neutrophils/*immunology , Spleen/*immunology, Animals ; Chemokine CXCL12/immunology ; Endothelial Cells/immunology ; Endothelial Cells/pathology ; Escherichia coli Infections/pathology ; Female ; Intercellular Adhesion Molecule-1/immunology ; Lung/pathology ; Mice ; Neutrophils/pathology ; Spleen/pathology |
| مستخلص: | The rapid response of neutrophils throughout the body to a systemic challenge is a critical first step in resolution of bacterial infection such as Escherichia coli ( E. coli ). Here we delineated the dynamics of this response, revealing novel insights into the molecular mechanisms using lung and spleen intravital microscopy and 3D ex vivo culture of living precision cut splenic slices in combination with fluorescent labelling of endogenous leukocytes. Within seconds after challenge, intravascular marginated neutrophils and lung endothelial cells (ECs) work cooperatively to capture pathogens. Neutrophils retained on lung ECs slow their velocity and aggregate in clusters that enlarge as circulating neutrophils carrying E. coli stop within the microvasculature. The absolute number of splenic neutrophils does not change following challenge; however, neutrophils increase their velocity, migrate to the marginal zone (MZ) and form clusters. Irrespective of their location all neutrophils capturing heat-inactivated E. coli take on an activated phenotype showing increasing surface CD11b. At a molecular level we show that neutralization of ICAM-1 results in splenic neutrophil redistribution to the MZ under homeostasis. Following challenge, splenic levels of CXCL12 and ICAM-1 are reduced allowing neutrophils to migrate to the MZ in a CD29-integrin dependent manner, where the enlargement of splenic neutrophil clusters is CXCR2-CXCL2 dependent. We show directly molecular mechanisms that allow tissue resident neutrophils to provide the first lines of antimicrobial defense by capturing circulating E. coli and forming clusters both in the microvessels of the lung and in the parenchyma of the spleen. 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 © 2021 Juzenaite, Secklehner, Vuononvirta, Helbawi, Mackey, Dean, Harker, Carlin, Rankin and De Filippo.) |
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| معلومات مُعتمدة: | A23983 United Kingdom CRUK_ Cancer Research UK; 23983 United Kingdom CRUK_ Cancer Research UK; 201356/Z/16/Z United Kingdom WT_ Wellcome Trust; A17196 United Kingdom CRUK_ Cancer Research UK; 201356/Z/16/Z United Kingdom CRUK_ Cancer Research UK |
| فهرسة مساهمة: | Keywords: E. coli challenge; intravascular neutrophils; intravital microscopy; neutrophil activation; splenic resident neutrophils |
| المشرفين على المادة: | 0 (Chemokine CXCL12) 0 (Cxcl12 protein, mouse) 0 (Icam1 protein, mouse) 126547-89-5 (Intercellular Adhesion Molecule-1) |
| تواريخ الأحداث: | Date Created: 20210506 Date Completed: 20210623 Latest Revision: 20240313 |
| رمز التحديث: | 20240313 |
| مُعرف محوري في PubMed: | PMC8089477 |
| DOI: | 10.3389/fimmu.2021.597595 |
| PMID: | 33953706 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1664-3224 |
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| DOI: | 10.3389/fimmu.2021.597595 |