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Lab Invest. 1998 May;78(5):591-602.

The interleukin-4/interleukin-13 receptor of human synovial fibroblasts: overexpression of the nonsignaling interleukin-13 receptor alpha2.

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1
Institute of Clinical Chemistry, University Hospital, Zurich, Switzerland.

Abstract

Interleukin (IL)-4 and IL-13 are known to bind to shared heteromultimeric receptor complexes of variable composition. Given the many regulatory effects of IL-4 and IL-13 on synovial cells, we aimed to characterize their IL-4/IL-13 receptor (R). Cultivated synovial fibroblasts expressed transcripts for IL-4Ralpha and IL-13Ralpha1, the human homolog of the recently cloned mouse IL-13R, but not the common gamma-chain of the IL-2R. In particular, IL-13Ralpha2 mRNA, encoding a different IL-13R recently cloned from human renal carcinoma cells, was expressed at a strikingly high level. Correspondingly, a predominant protein migrating at 65 to 75 kd was cross-linked by iodinated IL-13 and was not cross-competed by an excess of unlabeled IL-4. However, by flow cytofluorometry, IL-13Ralpha1 (detected by the anti-lL-13Ralpha1 mAb 65) and IL-4Ralpha (detected by the mAb S697) were expressed at similar low density. Radioligand binding studies revealed for both cytokines approximately 300 receptors/cell with similar high affinity. An additional class of IL-13Rs was identified after occupation of the shared high-affinity receptors by the nonsignaling, double-mutant IL-4121R-->D, 124Y-->D (RY-IL-4). In these experiments, 1251-IL-13 bound to a single receptor population with a Kd of approximately 300 pM and approximately 5000 sites/cell, matching the published affinity of monomeric IL-13Ralpha2 when expressed in COS7 cells. RY-IL-4 blocked the IL-4- and IL-13-mediated vascular cell adhesion molecule (VCAM)-1 expression and Stat6 activation, suggesting that the large number of high-affinity IL-13Ralpha2 monomers are silent receptors, likely representing a decoy target for IL-13.

PMID:
9605184
[Indexed for MEDLINE]
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