Interaction of interleukin 7 (IL-7) with glycosaminoglycans and its biological relevance.
We have investigated the binding of interleukin 7 (IL-7) to sulfated glycosaminoglycans and evaluated its biological consequences. IL-7 binds to heparin and heparan sulfate, to a lesser extent to dermatan sulfate and does not bind to chondroitin sulfate. It was eluted from heparin by 0.3-0.6 M NaCl and from heparan sulfate by < 0.3 M NaCl. We also measured the affinity of IL-7 for heparin using an affinity co-electrophoresis method and found an affinity of 25 nM. In spite of these findings, IL-7 does not bind to the S17 cell line which supports lymphopoiesis. However, addition of heparin to cultures of an IL-7-dependent pre-B cell line (2E8) inhibited IL-7-stimulated proliferation and IL-7 complexed with heparin was more resistant than free IL-7 to protease treatment. Taken together, these results suggest that heparin may act as a carrier for IL-7, blocking its interaction with target cells and protecting it from degradation during transit.
Clarke
D
D
Leukaemia Research Fund Centre, Institute of Cancer Research, London, UK.
Katoh
O
O
Gibbs
R V
RV
Griffiths
S D
SD
Gordon
M Y
MY
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002809:Chondroitin Sulfates / Q000378:metabolism; D002846:Chromatography, Affinity; D003871:Dermatan Sulfate / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006493:Heparin / Q000378:metabolism / Q000494:pharmacology; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D015851:Interleukin-7 / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D011485:Protein Binding
D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D010450:Endopeptidases; D006025:Glycosaminoglycans; D006493:Heparin; D006497:Heparan Sulfate; D015851:Interleukin-7