CXCR4 antagonist AMD3100 mobilizes leukocytes from bone marrow and thymus to blood in mice (HEM2P.265)

AMD3100 is approved for mobilizing hematopoietic stem cells to blood for transplantation in cancer by blocking chemokine receptor CXCR4. It also mobilizes mature leukocytes to blood; however, there is conflicting published evidence regarding the source of mobilized neutrophils (bone marrow vs lung), and the source(s) of other mobilized leukocytes is unknown. Here we used surgical, pharmacologic and histologic approaches to address these questions in mice. AMD3100 10 mg/kg sq mobilized the same leukocyte subsets to blood in mice as in humans, and increased neutrophil and monocyte content in lung and lymph node, while reducing neutrophil, lymphocyte and monocyte content in bone marrow as well as T cell content in thymus. Direct intrathymic labeling showed that AMD3100 mobilized naïve CD4+ and CD8+ T cells to blood. In contrast, splenectomy and experiments with FTY720, which blocks T cell egress from lymph node, suggested that spleen and lymph node were not major sources of AMD3100-mobilized cells. Importantly, AMD3100 did not inhibit neutrophil trafficking to thioglycollate-inflamed peritoneum. These data provide evidence that CXCR4 is a selective compartmentalization factor for both bone marrow (lymphocyte, monocyte, neutrophil) and thymus (naïve T cells), but is not critical for homeostatic trafficking of leukocytes to uninflamed tissues or for innate immune responses to inflamed sites, a profile that is favorable for chronic administration of AMD3100 in patients.