Recruitment of renal tubular epithelial cells expressing verotoxin-1 (Stx1) receptors in HIV-1 transgenic mice with renal disease.
BACKGROUND
Human immunodeficiency virus (HIV)-infected children are at risk of developing several renal parenchymal diseases, including hemolytic uremic syndrome (HUS). HUS is most frequently caused by infection with enteric Escherichia coli producing Shiga-like toxins (Stxs). In vitro studies have shown that cytokines known to be present at high systemic levels in HIV-1-infected children up-regulate the expression of the Stx glycolipid receptor (Gb3) in cultured endothelial cells. Thus, we studied whether HIV-1 or the HIV-associated "cytokine milieu" could modulate the expression of renal Stxs receptors in vivo.


METHODS
We used HIV-1 transgenic mice (HIV-Tg) expressing a deletion mutant of HIV-1 (pNL4-3). These mice develop renal disease similar to that of HIV-1-infected children. The expression of Gb3 was studied in renal sections from control and HIV-Tg mice by histochemistry, thin layer chromatography overlay studies, and high-pressure liquid chromatography.


RESULTS
By histochemistry, we found a significant recruitment of renal tubular epithelial cells expressing Gb3 in HIV-Tg mice with nephropathy, whereas kidneys from control mice showed limited staining in renal tubules. Gb3 was not found in glomeruli of either control or HIV-Tg mice. Thin layer chromatography overlay studies with Stxs and high-pressure liquid chromatography studies confirmed the marked elevation of Gb3 in HIV-Tg kidneys with renal disease.


CONCLUSIONS
These results suggest that the presence of HIV-associated nephropathy is associated with the recruitment of renal tubular epithelial cells expressing Stx1 receptors. The up-regulation of Stx1 receptors in HIV-diseased kidneys may increase the sensitivity of these cells to the cytotoxic effects of Stxs.
Liu
X H
XH
Children's Research Institute, Children's National Medical Center, Washington D.C., USA.
Lingwood
C A
CA
Ray
P E
PE
D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology; D015497:HIV-1 / Q000235:genetics*; D007668:Kidney / Q000378:metabolism; D007674:Kidney Diseases / Q000235:genetics / Q000378:metabolism*; D007684:Kidney Tubules / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics / Q000378:metabolism*; D012016:Reference Values; D022622:Shiga Toxin 1; D014018:Tissue Distribution / Q000502:physiology; D014281:Trihexosylceramides / Q000378:metabolism*