Heparan sulfate proteoglycans mediate interleukin-7-dependent B lymphopoiesis.
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.
Borghesi
L A
LA
Oklahoma Medical Research Foundation, Immunobiology and Cancer Program, Oklahoma City 73104, USA.
Yamashita
Y
Y
Kincade
P W
PW
D016475:3T3 Cells; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D016466:CHO Cells; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D006224:Cricetinae; D006131:Growth Inhibitors / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000502:physiology*; D006493:Heparin / Q000494:pharmacology; D006497:Heparan Sulfate / Q000378:metabolism / Q000494:pharmacology; D015851:Interleukin-7 / Q000378:metabolism / Q000502:physiology*; D019891:Leukopoiesis / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011485:Protein Binding; D017154:Stromal Cells / Q000378:metabolism
D006131:Growth Inhibitors; D019812:Heparan Sulfate Proteoglycans; D006493:Heparin; D006497:Heparan Sulfate; D015851:Interleukin-7