Differentiation and activation of eosinophils in the human bone marrow during experimental human endotoxemia.


Journal

Journal of leukocyte biology
ISSN: 1938-3673
Titre abrégé: J Leukoc Biol
Pays: England
ID NLM: 8405628

Informations de publication

Date de publication:
11 2020
Historique:
received: 09 10 2019
revised: 17 12 2019
accepted: 02 01 2020
pubmed: 11 1 2020
medline: 10 2 2021
entrez: 11 1 2020
Statut: ppublish

Résumé

Acute infection is characterized by eosinopenia. However, the underlying mechanism(s) are poorly understood and it is unclear whether decreased mobilization/production of eosinophils in the bone marrow (BM) and/or increased homing to the tissues play a role. The objective of this study was to investigate the differentiation and activation status of eosinophils in the human BM and blood upon experimental human endotoxemia, a standardized, controlled, and reproducible model of acute systemic inflammation. A BM aspirate and venous blood was obtained from seven healthy volunteers before, 4 h after, and 1 week after intravenous challenge with 2 ng/kg endotoxin. Early progenitors (CD34+/IL-5Rα+), eosinophil promyelocytes, myelocytes, metamyelocytes, and mature eosinophils were identified and quantified in the bone marrow and blood samples using flowcytometry based on specific eosinophil markers (CD193 and IL-5Rα). Activation status was assessed using antibodies against known markers on eosinophils: Alpha-4 (CD49d), CCR3 (CD193), CR1 (CD35), CEACAM-8 (CD66b), CBRM 1/5 (activation epitope of MAC-1), and by plasma cytokine analysis. Four hours after endotoxin administration, numbers of mature eosinophils in the blood and in the BM markedly declined compared with baseline, whereas numbers of all eosinophil progenitors did not change. The remaining eosinophils did not show signs of activation or degranulation despite significantly increased circulating levels of eotaxin-1. Furthermore, the expression of CD49d and CD193 on eosinophils was lower compared to baseline, but normalized after 7 days. Together these data imply that circulatory eosinopenia after an innate immune challenge is mediated by CD49d-mediated homing of eosinophils to the tissues.

Identifiants

pubmed: 31922294
doi: 10.1002/JLB.1AB1219-493R
doi:

Substances chimiques

Antigens, Differentiation 0

Types de publication

Clinical Trial Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1665-1671

Informations de copyright

© 2020 The Authors. Journal of Leukocyte Biology published by Wiley Periodicals, Inc. on behalf of Society for Leukocyte Biology.

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Auteurs

Marwan Hassani (M)

Department of Respiratory Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands.
Laboratory of Translational Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands.

Guus Leijte (G)

Department of Intensive Care and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.

Niklas Bruse (N)

Department of Intensive Care and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.

Matthijs Kox (M)

Department of Intensive Care and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.

Peter Pickkers (P)

Department of Intensive Care and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.

Nienke Vrisekoop (N)

Department of Respiratory Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands.
Laboratory of Translational Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands.

Leo Koenderman (L)

Department of Respiratory Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands.
Laboratory of Translational Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands.

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