From the Division of Rheumatology, The Children's Hospital of Philadelphia, Philadelphia, PA; the Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA; and the Department of Immunology, National Jewish Medical and Research Center, Denver, CO.
The chemokine receptor, CXCR4, serves as the primary coreceptor for entry of T-cell tropic human immunodeficiency virus (HIV). Binding of either the CXC-chemokine, stromal-derived factor 1
(SDF-1), or a CXCR4 antagonist, AMD3100, to CXCR4 inhibits infection of CD4+ T cells by T-tropic HIV-1, although only SDF-1 triggers T-cell signaling cascades. We have previously demonstrated that ligation of CD4 by T-cell tropic HIV-1 NL4-3 induces metalloproteinase-dependent L-selectin (CD62L) shedding on resting CD4+ T cells. However, the role of CXCR4 in HIV-induced L-selectin shedding is unclear. Here, we show that L-selectin shedding induced by HIV-1 NL4-3 is completely reversed by AMD3100, but not SDF-1, although SDF-1 alone does not induce L-selectin shedding. These results indicate that engagement of both CD4 and CXCR4 is required for HIV-induced shedding of L-selectin on primary resting CD4+ T cells.
Molecular and Clinical Epidemiology of CXCR4-Using HIV-1 in a Large Population of Antiretroviral-Naive Individuals
Impaired CXCR4 Signaling Contributes to the Reduced Neovascularization Capacity of Endothelial Progenitor Cells From Patients With Coronary Artery Disease
SDF-1/CXCR4 Axis Is Instrumental in Neointimal Hyperplasia and Recruitment of Smooth Muscle Progenitor Cells
Small peptide inhibitors of the CXCR4 chemokine receptor (CD184) antagonize the activation, migration, and antiapoptotic responses of CXCL12 in chronic lymphocytic leukemia B cells
Regulation of CXCR3 and CXCR4 expression during terminal differentiation of memory B cells into plasma cells
Identification of a human B-cell/myeloid common progenitor by the absence of CXCR4
Flt3 ligand and the Flt3 receptor regulate hematopoietic cell migration by modulating the SDF-1(CXCL12)/CXCR4 axis
WHIM syndromes with different genetic anomalies are accounted for by impaired CXCR4 desensitization to CXCL12
Chemokine receptor expression in EBV-associated lymphoproliferation in hu/SCID mice: implications for CXCL12/CXCR4 axis in lymphoma generation
Incorporation of CXCR4 into membrane lipid rafts primes homing-related responses of hematopoietic stem/progenitor cells to an SDF-1 gradient