Interleukin-5 binds to heparin/heparan sulfate. A model for an interaction with extracellular matrix.
Interleukin-5 (IL-5) is the major cytokine regulating eosinophil production. In allergic disease tissue damage is primarily caused by eosinophils. Heparan sulfate proteoglycans are components of the bone marrow stroma, which supports hemopoietic cell differentiation and proliferation. We show that at low IL-5 concentrations heparan sulfate enhances the proliferation of an IL-5-dependent cell line. To investigate a mechanism for this effect we used an artificial proteoglycan to establish an enzyme-linked immunosorbent assay for the binding of heparin to proteins. Using this assay we demonstrate that IL-5 binds to heparin. The IL-5/heparin interaction is inhibited by ethylenediaminetetraacetate and enhanced by low concentrations of zinc ions. IL-5 interacts with iduronic acid containing glycosaminoglycans, and heparan sulfate preparations that have numerous N-sulfated domains per chain are especially efficient at inhibiting heparin binding. Both IL-5/heparin binding and the synergistic effect of IL-5 and heparan sulfate on cell proliferation were inhibited by an anti-IL-5 monoclonal antibody. These data suggest that the binding of IL-5 to heparan sulfate modulates IL-5 activity.
Lipscombe
R J
RJ
TVW Telethon Institute for Child Health Research, Perth, Western Australia.
Nakhoul
A M
AM
Sanderson
C J
CJ
Coombe
D R
DR
D000818:Animals; D001665:Binding Sites; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005109:Extracellular Matrix / Q000502:physiology*; D017930:Genes, Reporter; D006493:Heparin / Q000737:chemistry / Q000378:metabolism*; D006497:Heparan Sulfate / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D006801:Humans; D015848:Interleukin-5 / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D008156:Luciferases / Q000096:biosynthesis; D051379:Mice; D008954:Models, Biological; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D013552:Swine; D014162:Transfection
D006493:Heparin; D006497:Heparan Sulfate; D015848:Interleukin-5; D008156:Luciferases; D011994:Recombinant Proteins