title: CXCR4 antagonist AMD3100 redistributes leukocytes from primary immune organs to secondary immune organs, lung, and blood in mice.
abstract: 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 h) the same leukocyte subsets to blood as in humans. Using this model, we found that AMD3100 mobilization of neutrophils, lymphocytes, and monocytes to blood is not 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.
authors: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors: Qian
authors: Q
authors: Liu
authors: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors: Zhanzhuo
authors: Z
authors: Li
authors: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors: Ji-Liang
authors: JL
authors: Gao
authors: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors: Wuzhou
authors: W
authors: Wan
authors: Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors: Sundar
authors: S
authors: Ganesan
authors: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors: David H
authors: DH
authors: McDermott
authors: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors: Philip M
authors: PM
authors: Murphy
mesh_terms: D000818:Animals; D001596:Benzylamines; D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects* / Q000276:immunology; D000080027:Cyclams; D005260:Female; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D016130:Immunophenotyping; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007958:Leukocyte Count; D007962:Leukocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D008168:Lung / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology; D051379:Mice; D010641:Phenotype; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology
chemical_list: D001596:Benzylamines; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; C088327:plerixafor
keywords: AMD3100; CXCR4; Cell trafficking; Leukocytes; Lymphoid organs; Mouse