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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)

  • Bruno Schnyder
  • Serena Lugli
  • Ningping Feng
  • Rene Moser
Part of the NATO ASI Series book series (NSSA, volume 294)

Abstract

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).

Keywords

Endothelial Cell Human Endothelial Cell Minor Extent Swiss Federal Institute Heterodimeric Complex 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 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

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Bruno Schnyder
    • 1
  • Serena Lugli
    • 1
  • Ningping Feng
    • 1
  • Rene Moser
    • 1
  1. 1.Institute of Toxicology of the Swiss Federal Institute of Technology and University of ZurichSchwerzenbachSwitzerland

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