Effect of the CXCR4 antagonist plerixafor on endogenous neutrophil dynamics in the bone marrow, lung and spleen
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Published version
Author(s)
Type
Journal Article
Abstract
Treatment with the CXCR4 antagonist, plerixafor (AMD3100), has been proposed for clinical use in patients with WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome and in pulmonary fibrosis. However, there is controversy with respect to the impact of plerixafor on neutrophil dynamics in the lung, which may affect its safety profile. In this study, we investigated the kinetics of endogenous neutrophils by direct imaging, using confocal intravital microscopy in mouse bone marrow, spleen, and lungs. Neutrophils are observed increasing their velocity and exiting the bone marrow following plerixafor administration, with a concomitant increase in neutrophil numbers in the blood and spleen, while the marginated pool of neutrophils in the lung microvasculature remained unchanged in terms of numbers and cell velocity. Use of autologous radiolabeled neutrophils and SPECT/CT imaging in healthy volunteers showed that plerixafor did not affect GM‐CSF‐primed neutrophil entrapment or release in the lungs. Taken together, these data suggest that plerixafor causes neutrophil mobilization from the bone marrow but does not impact on lung marginated neutrophil dynamics and thus is unlikely to compromise respiratory host defense both in humans and mice.
Date Issued
2020-06
Date Acceptance
2020-04-20
ISSN
0741-5400
Publisher
Wiley
Start Page
1175
End Page
1185
Journal / Book Title
Journal of Leukocyte Biology
Volume
107
Issue
6
Copyright Statement
© 2020 The Authors. Journal of Leukocyte Biology published by Wiley Periodicals, Inc. on behalf of Society for Leukocyte Biology
This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Sponsor
Wellcome Trust
Identifier
https://jlb.onlinelibrary.wiley.com/doi/full/10.1002/JLB.1MA0420-571RR
Grant Number
201356/Z/16/Z
Subjects
Science & Technology
Life Sciences & Biomedicine
Cell Biology
Hematology
Immunology
neutrophil activation
neutrophil dynamics
neutrophil mobilization
CHEMOKINE RECEPTOR
RAPID MOBILIZATION
WHIM-SYNDROME
AMD3100
CELLS
RELEASE
MYELOKATHEXIS
RECRUITMENT
INHIBITION
PLATFORM
neutrophil activation
neutrophil dynamics
neutrophil mobilization
Immunology
0601 Biochemistry and Cell Biology
1107 Immunology
Publication Status
Published
Date Publish Online
2020-05-06