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Articles in PresS, published online ahead of print August 8, 2001
Am J Physiol Renal Physiol, 10.1152/ajprenal.0102.2001
Submitted on March 23, 2001
Accepted on August 3, 2001
1 Pathology, Academic Medical Center, Amsterdam, Netherlands
2 Cell Physiology, Academic Medical Center, Amsterdam, Netherlands
3 Institute of Physiological Chemistry, Martin Luther University Halle-Wittenberg, Halle, Germany
* To whom correspondence should be addressed. E-mail: j.g.vandenberg{at}amc.uva.nl.
Minimal change nephrosis (MCN) is characterized by massive proteinuria and ultrastructural alterations of glomerular visceral epithelial cells (GVEC). MCN has been associated with elevated production of interleukin(IL)-13 by circulating T-lymphocytes and with T-helper-2 lymphocyte-dependent conditions. We recently showed that GVEC express IL-4/IL-13 receptors and that IL-4 and IL-13 increase transcellular ion transport over GVEC monolayers. We therefore hypothesized that IL-13 may directly injure GVEC. Here we demonstrate that IL-4 and IL-13 induce bafilomycin A1-sensitive basolateral proton secretion by cultured GVEC, indicating involvement of the vacuolar H+-ATPase. The effects of IL-4 and IL-13 were accompanied by redistribution of small GTPases Rab5b and Rab7, as shown by confocal immunofluorescence studies. Furthermore, Western blot analysis and assays for cysteine proteinase activity revealed basolateral secretion of the lysosomal proteinase procathepsin L by cultured GVEC, stimulated by IL-4 and IL-13. We speculate that IL-4 and IL-13 influence intracellular trafficking of proteins and promote proteolysis at the basolateral surface of GVEC, which may play a pathogenic role in altered glomerular permeability.
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