The CXCR4 antagonist AMD3100 redistributes leukocytes from primary immune organs to secondary immune organs lung and blood in mice

摘要

AMD3100 (plerixafor), is a specific CXCR4 antagonist approved by the FDA for mobilizing hematopoietic stem cells from bone marrow to blood for transplantation in cancer. AMD3100 also mobilizes most mature leukocyte subsets to blood; however, their source and trafficking potential have not been fully delineated. Here, we show that a single injection of AMD3100 10 mg/kg into C57Bl/6 mice rapidly mobilizes (peak ~ 2.5 hours) the same leukocyte subsets to blood as in humans. Using this model, we found that AMD3100 mobilization of neutrophils, lymphocytes and monocytes to blood isn’t reduced by splenectomy or by blockade of lymphocyte egress from lymph node with FTY720, but is coupled to i) reduced content of each of these cell types in the bone marrow; ii) reduced T-cell numbers in thymuses; iii) increased lymphocytes in lymph nodes; and iv) increased neutrophil and monocyte content in the lung. Direct intrathymic labeling showed that AMD3100 selectively mobilizes naïve thymic CD4⁺ and CD8⁺ T cells to blood. Finally, AMD3100-induced neutrophil mobilization to blood did not reduce neutrophil trafficking to thioglycollate-inflamed peritoneum. Thus, AMD3100 redistributes lymphocytes, monocytes and neutrophils from primary immune organs to secondary immune organs, peripheral tissues and blood, without compromising neutrophil trafficking to inflamed sites.