We hypothesized that a small molecule CXCR4 antagonist, AMD3100 (AMD), could augment the mobilization of bone marrow (BM)-derived endothelial progenitor cells (EPCs), thereby enhancing neovascularization and functional recovery after myocardial infarction. Single-dose AMD injection administered after the onset of myocardial infarction increased circulating EPC counts and myocardial vascularity,...

Asthmatic responses are associated with the lung homing of bone marrow (BM)-derived progenitors implicated as effectors of disease pathology. Studies have shown that increases in lung extracted vascular endothelial progenitor cells (VEPCs) correlate with airway angiogenesis and declining lung function. We investigated the effect of modulating lung homing of VEPCs on tissue remodelling and airwa...

CXCR4 is a G protein-coupled receptor for stromal-derived factor 1 (SDF-1) that plays a critical role in leukocyte trafficking, metastasis of mammary carcinoma, and human immunodeficiency virus type-1 infection. To elucidate the mechanism for CXCR4 activation, a constitutively active mutant (CAM) was derived by coupling the receptor to the pheromone response pathway in yeast. Conversion of Asn-...

CXCR4 is a G protein-coupled receptor (GPCR) that has multiple critical functions in normal and pathologic physiology that include regulation of the metastatic behavior of mammary carcinoma, and utilization as a coreceptor for infection by T-tropic strains of human immunodeficiency virus-1. Molecular dynamic simulations of the rhodopsin-based homology model of CXCR4 were performed in a solvated...

RESULTS—CXCR4 is expressed in -cells, and SDF-1 is expressed in microvascular endothelial cells within the islets and in surrounding interstitial stromal tissue. Transgenic mice overexpressing SDF-1 within their -cells (RIP-SDF-1 mice) are resistant to STZ-induced -cell apoptosis and diabetes. In MIN6 -cells, a CXCR4 antagonist (AMD3100) induces apoptosis, increases reactive oxygen species, dec...

A CXCR4 inhibitor-resistant HIV-1 was isolated from a dual-X4 HIV-1 in vitro. The resistant variant displayed competitive resistance to the CXCR4 inhibitor AMD3100, indicating that the resistant variant had a higher affinity for CXCR4 than that of the wild-type HIV-1. Amino acid sequence analyses revealed that the resistant variant harbored amino acid substitutions in the V2, C2, and C4 regions...

The chemokine receptor CXCR4 and its cognate ligand CXCL12 are pivotal for establishing metastases from many tumor types. Thus, CXCR4 may offer a cell surface target for molecular imaging of metastases, assisting diagnosis, staging, and therapeutic monitoring. Furthermore, noninvasive detection of CXCR4 status of a primary tumor may provide an index of the metastatic potential of the lesion. He...

The coreceptors used by primary syncytium-inducing (SI) human immunodeficiency virus type 1 isolates for infection of primary macrophages were investigated. SI strains using only CXCR4 replicated equally well in macrophages with or without CCR5 and were inhibited by several different ligands for CXCR4 including SDF-1 and bicyclam derivative AMD3100. SI strains that used a broad range of corecep...

Abstract Placental dysfunction originates during placental development, specifically the events of placentation. Vascularization is a key component placentation due to its role in fetal-maternal exchange. Cytokines are regulators development; signaling chemokine ligand 12 (CXCL12) and receptor (CXCR4) drives vascularization. Utilizing an vivo sheep model, we demonstrated that suppressing CXCL12...

AMD3100 (Plerixafor), a specific antagonist of CXCR4, is the most potent small molecule non-peptide inhibitor to CXCR4/CXCL12 axis. The chemokine receptor CXCR4 and its ligand CXCL12 (SDF-1) expressed in variety tumor cells play an important role regulating biological behavior. microenvironment (TME) environment around tumor, comprising blood vessels, immune cells, fibroblasts, signaling molecu...