Identification, purification, and characterization of a soluble interleukin (IL)-13-binding protein. Evidence that it is distinct from the cloned Il-13 receptor and Il-4 receptor alpha-chains.
Interleukin-4 (IL-4) and interleukin-13 (IL-13) are structurally and functionally related cytokines which play an important role in the regulation of the immune response to infection. The functional similarity of IL-4 and IL-13 can be explained, at least in part, by the common components that form their cell surface receptors, namely the IL-4 receptor alpha-chain (IL-4Ralpha) and the IL-13 receptor alpha-chain (IL-13Ralpha). Soluble forms of the IL-4Ralpha have also been described and implicated in modulating the effect of IL-4. In this paper we describe the presence of a 45,000-50,000 Mr IL-13-binding protein (IL-13BP) in the serum and urine of mice. This protein binds IL-13 with a 100-300-fold higher affinity (KD = 20-90 pM) than does the cloned IL-13Ralpha (KD = 3-10 nM). In addition to this functional difference, the IL-13BP appears to be structurally and antigenically distinct from the IL-13Ralpha. Finally, unlike the cloned receptor, the IL-13BP acts as a potent inhibitor of IL-13 binding to its cell surface receptor, raising the possibility that it may be used to modulate the effects of IL-13 in vivo.
Zhang
J G
JG
Walter and Eliza Hall Institute of Medical Research and the Cooperative Research Centre for Cellular Growth Factors, P.O. Royal Melbourne Hospital, Victoria 3050, Australia.
Hilton
D J
DJ
Willson
T A
TA
McFarlane
C
C
Roberts
B A
BA
Moritz
R L
RL
Simpson
R J
RJ
Alexander
W S
WS
Metcalf
D
D
Nicola
N A
NA
D000818:Animals; D015703:Antigens, CD / Q000737:chemistry* / Q000235:genetics; D002846:Chromatography, Affinity; D002850:Chromatography, Gel; D003001:Cloning, Molecular; D004591:Electrophoresis, Polyacrylamide Gel; D006031:Glycosylation; D018793:Interleukin-13 / Q000378:metabolism* / Q000652:urine; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4 / Q000378:metabolism*; D051379:Mice; D008970:Molecular Weight; D011817:Rabbits; D018123:Receptors, Interleukin / Q000032:analysis* / Q000737:chemistry* / Q000235:genetics; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; D012697:Serine Endopeptidases / Q000378:metabolism
D015703:Antigens, CD; C508183:Il13ra1 protein, mouse; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; D015847:Interleukin-4; D012697:Serine Endopeptidases; C028344:glutamyl endopeptidase