IL-4 and IL-13 Bind to a Shared Heterodimeric Complex on Endothelial Cells Mediating Induction of VCAM-1 in the Absence of the Common γ Chain (γc)
IL-4 and IL-13 exert similar, non-additive effects on endothelial cells, inducing VCAM-1 expression and subsequent transmigration of eosinophils. The receptor (R) for IL-4 and IL-13 was described as a shared heteromultimeric complex in which the γc subunit was essential for activity. Endothelial cells bound both cytokines with high affinity; by flow cytoflourometry and RT-PCR expressed IL-4Rα but not the γc of the IL-2R, which has previously been reported to participate in the IL-4R complex of different hematopoietic cells. Radioligand crosslinking experiments followed by immunoprecipitation with the mAb S697 to the IL-4Rα showed IL-4-specific binding at 130 kDa, the IL-4Rα, and to a minor extent to a double band co-immunoprecipitated at 65–75 kDA. [125I]IL-13 bound predominantly to that 65–75 kDa and with a trace amount at 130 kDa. However, with [125I]IL-13, no ligand crosslinked receptor was precipitated by the mAb S697 indicating an individual IL-13 binding subunit. The finding that excess unlabeled IL-4 completely displaced IL-13 binding suggests shared receptor subunits. Similarly, non-signaling IL-4 (Y124D)-mutant abolished IL-4 and IL-13 mediated signal transduction. The mAb TUGh4, specific for the γc, failed to precipitate ligant-crosslinked IL-4- and IL-13R’s. In summary, the data show that on human endothelial cells, the receptor for IL-4 and IL-13 is heterodimeric complex of the IL-4Rα and 65–75 kD IL-13 binding protein, the putative IL-13α (1).
KeywordsEndothelial Cell Human Endothelial Cell Minor Extent Swiss Federal Institute Heterodimeric Complex
- 1.Schnyder, B., S. Lugli, N.P. Feng, H. Etter, R.A. Lutz, B. Ryffel, K. Sugamura, H. Wunderli-Allenspach, and R. Moser. 1996, Interleukin-4(IL-4) and IL-13 bind to a shared heterodimeric complex on endothelial cells mediating vascular cell adhesion molecule-1 induction in the absence of the common gamma chain. Blood, 87(10):4286–4295.PubMedGoogle Scholar