Abstract
Stromal-derived factor-1alpha (SDF-1alpha), the high-affinity ligand of CXC-chemokine receptor 4 (CXCR4), induced a progressive increase of apoptosis when added to the Jurkat CD4+/CXCR4+ T cell line. The SDF-1alpha-mediated Jurkat cell apoptosis was observed in serum-free or serum-containing cultures, peaked at SDF-1alpha concentrations of 10-100 ng/ml, required 3 days to take place, and was completely blocked by the z-VAD-fmk tripeptide caspase inhibitor. Although SDF-1alpha did not modify the expression of TNF-alpha or that of TNF-RI and TNF-RII, it increased the expression of surface Fas/APO-1 (CD95) and intracellular Fas ligand (CD95L) significantly. Moreover, the ability of SDF-1alpha to induce apoptosis was inhibited by an anti-CD95 Fab' neutralizing antibody. These findings suggest a role for SDF-1alpha in the homeostatic control of CD4+ T-cell survival/apoptosis mediated by the CD95-CD95L pathway.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Chloromethyl Ketones / pharmacology
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Antibodies, Blocking / pharmacology
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Apoptosis / drug effects
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Apoptosis / immunology*
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CD4-Positive T-Lymphocytes / cytology*
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism
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Caspase Inhibitors
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Cell Line, Transformed
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Cell Membrane / immunology
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Cell Membrane / metabolism
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Chemokine CXCL12
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Chemokines, CXC / antagonists & inhibitors
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Chemokines, CXC / physiology*
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Cysteine Proteinase Inhibitors / pharmacology
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Fas Ligand Protein
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Humans
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Immune Sera / pharmacology
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Intracellular Fluid / immunology
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Intracellular Fluid / metabolism
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Jurkat Cells / cytology
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Jurkat Cells / drug effects
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Jurkat Cells / immunology
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Jurkat Cells / metabolism
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Ligands
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Lymphocyte Activation
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Membrane Glycoproteins / antagonists & inhibitors
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Membrane Glycoproteins / biosynthesis*
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Membrane Glycoproteins / physiology
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Receptors, Tumor Necrosis Factor / biosynthesis
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Signal Transduction / immunology*
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Stromal Cells / immunology
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Tumor Necrosis Factor-alpha / biosynthesis
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Up-Regulation / immunology*
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fas Receptor / biosynthesis*
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fas Receptor / immunology
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fas Receptor / physiology
Substances
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Amino Acid Chloromethyl Ketones
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Antibodies, Blocking
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CXCL12 protein, human
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Caspase Inhibitors
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Chemokine CXCL12
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Chemokines, CXC
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Cysteine Proteinase Inhibitors
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FASLG protein, human
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Fas Ligand Protein
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Immune Sera
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Ligands
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Membrane Glycoproteins
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Receptors, Tumor Necrosis Factor
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Tumor Necrosis Factor-alpha
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benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
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fas Receptor