普乐沙福
CXCR4拮抗剂
脾脏
骨髓
肺
CXCR4型
免疫学
病理
医学
生物
药理学
内科学
炎症
趋化因子
作者
Janesh Pillay,Nicola Tregay,Goda Juzenaite,Leo M. Carlin,Chiara Pirillo,David Gaboriau,Neda Farahi,Charlotte Summers,Cristina Lo Celso,Edwin R. Chilvers,Sara M. Rankin,Katia De Filippo
标识
DOI:10.1002/jlb.1ma0420-571rr
摘要
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.
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