Np. Feng et al., THE INTERLEUKIN-4 INTERLEUKIN-13 RECEPTOR OF HUMAN SYNOVIAL FIBROBLASTS - OVEREXPRESSION OF THE NONSIGNALING INTERLEUKIN-13 RECEPTOR ALPHA-2/, Laboratory investigation, 78(5), 1998, pp. 591-602
Citations number
58
Categorie Soggetti
Pathology,"Medical Laboratory Technology","Medicine, Research & Experimental
Interleukin (IL)-4 and IL-13 are known to bind to shared heteromultime
ric receptor complexes of variable composition. Given the many regulat
ory effects of IL-4 and IL-13 on synovial cells, we aimed to character
ize their IL-4/IL-13 receptor (R). Cultivated synovial fibroblasts exp
ressed transcripts for IL-4R alpha and IL-13R alpha 1, the human homol
og of the recently cloned mouse IL-13R, but not the common gamma-chain
of the IL-2R. In particular, IL-13R alpha 2 mRNA, encoding a differen
t IL-13R recently cloned from human renal carcinoma cells, was express
ed at a strikingly high level. Correspondingly, a predominant protein
migrating at 65 to 75 kd was cross-linked by iodinated IL-13 and was n
ot cross-competed by an excess of unlabeled IL-4. However, by flow cyt
ofluorometry, IL-13R alpha 1 (detected by the anti-IL-13R alpha 1 mAb
65) and IL-4R alpha (detected by the mAb S697) were expressed at simil
ar low density. Radioligand binding studies revealed for both cytokine
s approximately 300 receptors/cell with similar high affinity. An addi
tional class of IL-13Rs was identified after occupation of the shared
high-affinity receptors by the nonsignaling, double-mutant IL-4(121)R-
->D, Y-124-->D (RY-IL-4). In these experiments, (HL)-H-125-13 bound to
a single receptor population with a K-d of approximately 300 pM and a
pproximately 5000 sites/cell, matching the published affinity of monom
eric IL-13R alpha 2 when expressed in COS7 cells. RY-IL-4 blocked the
IL-4- and IL-13-mediated vascular cell adhesion molecule (VCAM)-1 expr
ession and Stat6 activation, suggesting that the large number of high-
affinity IL-13R alpha 2 monomers are silent receptors, likely represen
ting a decoy target for IL-13.