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Stromal derived factor-1 alpha (SDF-1 alpha) induces CD4+ T cell apoptosis via the functional up-regulation of the Fas (CD95)/Fas ligand (CD95L) pathway.
- Source :
-
Journal of leukocyte biology [J Leukoc Biol] 2001 Feb; Vol. 69 (2), pp. 263-70. - Publication Year :
- 2001
-
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.
- Subjects :
- Amino Acid Chloromethyl Ketones pharmacology
Antibodies, Blocking pharmacology
Apoptosis drug effects
CD4-Positive T-Lymphocytes metabolism
Caspase Inhibitors
Cell Line, Transformed
Cell Membrane immunology
Cell Membrane metabolism
Chemokine CXCL12
Chemokines, CXC antagonists & inhibitors
Cysteine Proteinase Inhibitors pharmacology
Fas Ligand Protein
Humans
Immune Sera pharmacology
Intracellular Fluid immunology
Intracellular Fluid metabolism
Jurkat Cells cytology
Jurkat Cells drug effects
Jurkat Cells immunology
Jurkat Cells metabolism
Ligands
Lymphocyte Activation
Membrane Glycoproteins antagonists & inhibitors
Membrane Glycoproteins physiology
Receptors, Tumor Necrosis Factor biosynthesis
Stromal Cells immunology
Tumor Necrosis Factor-alpha biosynthesis
fas Receptor immunology
fas Receptor physiology
Apoptosis immunology
CD4-Positive T-Lymphocytes cytology
CD4-Positive T-Lymphocytes immunology
Chemokines, CXC physiology
Membrane Glycoproteins biosynthesis
Signal Transduction immunology
Up-Regulation immunology
fas Receptor biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 0741-5400
- Volume :
- 69
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of leukocyte biology
- Publication Type :
- Academic Journal
- Accession number :
- 11272277