Cell-surface trafficking and release of flt3 ligand from T lymphocytes is induced by common cytokine receptor gamma-chain signaling and inhibited by cyclosporin A
| Autor: | Lukas Landmann, Christoph Rahner, Otmar Pfister, Catherine Nissen, Aleksandra Wodnar-Filipowicz, Elena Chklovskaia |
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| Rok vydání: | 2001 |
| Předmět: |
Male
Transplantation Conditioning Pancytopenia medicine.medical_treatment T-Lymphocytes Golgi Apparatus Lymphocyte Activation Biochemistry Cyclosporin a Child Hematopoietic Stem Cell Transplantation Hematology Middle Aged Haematopoiesis Protein Transport Cytokine Interleukin 15 Child Preschool Hematologic Neoplasms Cyclosporine Cytokines Female Cytokine receptor Immunosuppressive Agents medicine.drug Interleukin 2 Adult medicine.medical_specialty Adolescent Immunology Biology Transplantation Autologous Internal medicine medicine Humans Transplantation Homologous Receptors Cytokine Interleukin 4 Aged Interleukin-7 T-cell receptor Cell Membrane Membrane Proteins Cell Biology Molecular biology Hematopoiesis Endocrinology Interleukin-2 Interleukin-4 Interleukin-5 |
| Zdroj: | Macquarie University |
| ISSN: | 0006-4971 |
| Popis: | The flt3 ligand (FL) is a growth and differentiation factor for primitive hematopoietic precursors, dendritic cells, and natural killer cells. Human T lymphocytes express FL constitutively, but the cytokine is retained intracellularly within the Golgi complex. FL is mobilized from the cytoplasmic stores and its serum levels are massively increased during the period of bone marrow aplasia after stem cell transplantation (SCT). Signals that trigger the release of FL by T cells remain unknown. This study shows that interleukin (IL)-2, IL-4, IL-7, and IL-15, acting through a common receptor γ chain (γc), but not cytokines interacting with other receptor families, are efficient inducers of cell surface expression of membrane-bound FL (mFL) and secretion of soluble FL (sFL) by human peripheral blood T lymphocytes. The γc-mediated signaling up-regulated FL in a T-cell receptor-independent manner. IL-2 and IL-7 stimulated both FL messenger RNA (mRNA) expression and translocation of FL protein to the cell surface. Cyclosporin A (CsA) inhibited γc-mediated trafficking of FL at the level of transition from the Golgi to the trans-Golgi network. Accordingly, serum levels of sFL and expression of mFL by T cells of CsA-treated recipients of stem cell allografts were reduced approximately 2-fold (P |
| Databáze: | OpenAIRE |
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