Pillay, J. et al. (2020) Effect of the CXCR4 antagonist plerixafor on endogenous neutrophil dynamics in the bone marrow, lung and spleen. Journal of Leukocyte Biology, 107(6), pp. 1175-1185. (doi: 10.1002/JLB.1MA0420-571RR) (PMID:32374077)
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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.
| Item Type: | Articles |
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| Additional Information: | This work was funded by a grant provided to J.P. by the Lung Foundation Netherlands (5.2.14.058JO), the NIHR Cambridge Biomedical Research Centre and NIHR Imperial Biomedical Research Centre. E.R.C. and C.S.’ laboratories received grant support from the Medical Research Council, Wellcome Trust, NIHR, GlaxoSmithKline, MedImmune Ltd., and Bristol‐Myers Squibb. C.L.C. was supported by Bloodwise (12033), CRUK (C36195/A1183) and European Research Council (ERC) (337066). C.P. was supported by Bloodwise (12033). The Facility for Imaging by Light Microscopy (FILM) at Imperial College London was part‐supported by funding from the Wellcome Trust (grant 104931/Z/14/Z) and BBSRC (grant BB/L015129/1). K.D.F. was supported by funding from the Wellcome Trust (201356/Z/16/Z). L.M.C. was supported by core funding from Cancer Research UK (A23983 and A17196). |
| Keywords: | Neutrophil activation, neutrophil dynamics, neutrophil mobilization. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Carlin, Dr Leo |
| Authors: | Pillay, J., Tregay, N., Juzenaite, G., Carlin, L. M., Pirillo, C., Gaboriau, D. C.A., Farahi, N., Summers, C., Lo Celso, C., Chilvers, E. R., Rankin, S., and De Filippo, K. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | Journal of Leukocyte Biology |
| Publisher: | Wiley |
| ISSN: | 0741-5400 |
| ISSN (Online): | 1938-3673 |
| Published Online: | 06 May 2020 |
| Copyright Holders: | Copyright © 2020 The Authors |
| First Published: | First published in Journal of Leukocyte Biology 107(6): 1175-1185 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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