Effect of the CXCR4 antagonist plerixafor on endogenous neutrophil dynamics in the bone marrow, lung and spleen

Janesh Pillay, Nicola Tregay, Goda Juzenaite, Leo M Carlin, Chiara Pirillo, David C A Gaboriau, Neda Farahi, Charlotte Summers, Cristina Lo Celso, Edwin R Chilvers, Sara Rankin, Katia De Filippo

    Research output: Contribution to journalArticleAcademicpeer-review

    8 Citations (Scopus)
    32 Downloads (Pure)

    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.

    Original languageEnglish
    Pages (from-to)1175-1185
    Number of pages11
    JournalJournal of Leukocyte Biology
    Volume107
    Issue number6
    DOIs
    Publication statusPublished - Jun-2020

    Keywords

    • Animals
    • Bone Marrow/diagnostic imaging
    • Cell Tracking/methods
    • Female
    • Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology
    • Hematopoietic Stem Cell Mobilization/methods
    • Hematopoietic Stem Cells/cytology
    • Heterocyclic Compounds/pharmacology
    • Humans
    • Leukocyte Count
    • Lung/cytology
    • Mice, Inbred C57BL
    • Neutrophils/cytology
    • Radiopharmaceuticals/administration & dosage
    • Single Photon Emission Computed Tomography Computed Tomography
    • Spleen/cytology
    • Technetium/administration & dosage

    Cite this