A soluble, high-affinity, interleukin-4-binding protein is present in the biological fluids of mice.
Cytokines such as interleukin 4 (IL-4) play a key role in the regulation of immune responses, but little is known about how their multiple activities are regulated in vivo. In this report, we demonstrated that an IL-4-binding protein (IL-4BP) is constitutively present in the biological fluids of mice (serum, ascites, fluid, and urine). Binding of 125I-labeled IL-4 to the IL-4BP is specific and saturable and can be inhibited by an excess of unlabeled IL-4 but not IL-2. The IL-4BP binds IL-4 with an affinity similar to that reported for the cellular IL-4 receptor (Kd approximately 7 x 10(-11) M) and has a molecular mass of 30-40 kDa and pI values of 3.6-4.8. IL-4BP-containing biological fluids or purified IL-4BP competitively inhibit the binding of 125I-labeled IL-4 to mouse T or B cells and inhibit the biological activity of IL-4 but not IL-2. The serum levels of IL-4BP in severe combined immunodeficiency (SCID) mice are lower than those of normal mice. The above findings suggest that IL-4BP plays an important immunoregulatory role in vivo.
Fernandez-Botran
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Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235.
Vitetta
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D000818:Animals; D001201:Ascites / Q000378:metabolism; D001327:Autoimmune Diseases / Q000378:metabolism; D015704:CD4 Antigens / Q000276:immunology; D002352:Carrier Proteins / Q000097:blood / Q000302:isolation & purification / Q000378:metabolism*; D003432:Cross-Linking Reagents; D007153:Immunologic Deficiency Syndromes / Q000378:metabolism; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007518:Isoantibodies / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D008970:Molecular Weight; D011485:Protein Binding
D015704:CD4 Antigens; D002352:Carrier Proteins; D003432:Cross-Linking Reagents; D007518:Isoantibodies; D015847:Interleukin-4