Details

Autor(en) / Beteiligte

• BORGHESI, L. A
• YAMASHITA, Y
• KINCADE, P. W

Titel

Heparan sulfate proteoglycans mediate interleukin-7-dependent B lymphopoiesis

Ist Teil von

• Blood, 1999, Vol.93 (1), p.140-148

Ort / Verlag

Washington, DC: The Americain Society of Hematology

Erscheinungsjahr

1999

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.