Heparan Sulfate Proteoglycans Mediate Interleukin-7– Dependent B Lymphopoiesis
| Autor: | Yoshio Yamashita, Lisa A. Borghesi, Paul W. Kincade |
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| Rok vydání: | 1999 |
| Předmět: | |
| Zdroj: | Blood. 93:140-148 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v93.1.140.401k40_140_148 |
| Popis: | Heparin/heparan sulfate proteoglycans (HSPGs) have the potential to bind and directly regulate the bioactivity of hematopoietic growth factors including interleukin-7 (IL-7), a cytokine critical for murine B-cell development. We examined the consequence of manipulating soluble heparin and cell-surface heparan sulfate to IL-7–dependent responses of B-cell precursors. Soluble heparin was found to inhibit production of lymphoid, but not myeloid, cells in long-term bone marrow cultures. Analysis of pro-B cells lacking plasma membrane HS suggests that this glycosaminoglycan is required for efficient binding and responsiveness to IL-7. By contrast, responses of hematopoietic cells to other cytokines were not influenced by heparin addition or HS removal. Therefore, HSPGs on B-lineage precursors may function as IL-7 receptor components similar to HSPGs known to be important for the bFGF receptor. Other experiments suggest that HSPGs on the surface of stromal cells provide a weakly associating docking site for IL-7, possibly controlling availability of this cytokine to B-cell precursors. Together these data demonstrate a direct role for heparinlike molecules in regulating the IL-7–dependent stages of murine B lymphopoiesis. |
| Databáze: | OpenAIRE |
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