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Promotion of cell adherence and spreading: a novel function of RAGE, the highly selective differentiation marker of human alveolar epithelial type I cells

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Abstract

The receptor for advanced glycation endproducts (RAGE) is expressed under pathological conditions in many tissues and has been assigned many functions. We demonstrate, in normal human lung tissue, the preferential and highly abundant expression of RAGE by quantitative polymerase chain reaction. In addition, RAGE expression, as a specific differentiation marker of alveolar epithelial type I cells (AT I cells), and its localization to the basolateral plasma membrane have been confirmed by means of newly raised monoclonal antibodies. The physiological function of RAGE on AT I cells has previously remained elusive. By using HEK293 cells transfected with cDNA encoding for full-length RAGE, we show that RAGE enhances the adherence of epithelial cells to collagen-coated surfaces and has a striking capacity for inducing cell spreading. The preferential binding of RAGE to collagen has been confirmed by assaying the binding of soluble RAGE to various substrates. RAGE might thus assist AT I cells to acquire a spreading morphology, thereby ensuring effective gas exchange and alveolar stability.

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Abbreviations

AGE:

advanced glycation endproducts

AT I/II:

alveolar epithelial type I/II cells

CML:

carboxymethyllysine

FI:

fluorescence intensity

hAEpC:

human alveolar epithelial cells

HUVEC:

human umbilical vein endothelial cells

KGF:

keratinocyte growth factor, -/- mouse: knockout mouse

PI:

propidium iodide

SP-C/D:

surfactant protein C/D

sRAGE:

soluble RAGE

RAGE:

receptor for AGE

TEER:

transepithelial electrical resistance

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Acknowledgements

We thank Dr. M. A. Shearman (Merck, Sharp & Dome, Essex, UK) for kindly providing the polyclonal goat anti-RAGE serum, and Dr. S. E. Gabriel (Chapel Hill, USA) for providing the polyclonal rabbit anti-aquaporin-5 antiserum. We are also grateful to Sylvia Großklaus for isolating HUVEC, to Christine Graefe and Heidi Gebauer for immunizing mice and cultivating the hybridoma cells, and to Ms. Susanne Kossek and Ms. Katja Klein for their skilful technical assistance. Last but not least, our special thanks go to Dr. M. Bachmann (Dresden, Germany) for carefully reading the manuscript and for his inspiring discussions.

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Authors and Affiliations

  1. Institute of Immunology, Medical Faculty, Technical University of Dresden, Fetscherstrasse 42, 01307, Dresden, Germany

    Nina Demling & Ernst Peter Rieber

  2. Department of Biopharmaceutics and Pharmaceutical Technology, Saarland University, 66123, Saarbrücken, Germany

    Carsten Ehrhardt

  3. School of Pharmacy, Pharmaceutics and Pharmaceutical Technology, Trinity College, University of Dublin, Dublin 2, Ireland

    Carsten Ehrhardt

  4. Institute of Anatomy, Technical University of Dresden, Fetscherstrasse 74, 01307, Dresden, Germany

    Michael Kasper & Lilla Knels

  5. Center for Electron Microscopy, Medical Faculty, Saarland University, 66421, Homburg, Germany

    Michael Laue

  6. Department of Anesthesiology, Technical University of Dresden, University Hospital Carl Gustav Carus, 01307, Dresden, Germany

    Lilla Knels

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  1. Nina Demling
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  2. Carsten Ehrhardt
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Correspondence to Ernst Peter Rieber.

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This work was in part supported by grants from Saxonian Ministry for Science and Arts (AZ: 4-7531.50-03-0370-01/7) to N.D. and a “Förderung des wissenschaftlichen Nachwuchses” grant from the DPhG to C.E.

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Demling, N., Ehrhardt, C., Kasper, M. et al. Promotion of cell adherence and spreading: a novel function of RAGE, the highly selective differentiation marker of human alveolar epithelial type I cells. Cell Tissue Res 323, 475–488 (2006). https://doi.org/10.1007/s00441-005-0069-0

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