Enhanced tubular epithelial CD44 expression in MRL-lpr lupus nephritis.
The cell surface glycoprotein CD44 is expressed by cells of hematopoietic origin and constitutes a receptor for hyaluronic acid and matrix proteins. Because CD44 could play a role in recruiting inflammatory cells to sites of immune injury, we examined the renal CD44 expression in normal and in autoimmune MRL-lpr mice by immunohistochemistry and at a molecular level. In normal kidneys, immunoperoxidase staining for CD44 is restricted to interstitial cells and certain urothelial cells. In nephritic MRL-lpr, CD44 expression is prominent in perivascular inflammatory infiltrates and in glomerular crescents. Interestingly, CD44 is also focally expressed by cortical tubular epithelial cells (TEC) in nephritic MRL-lpr kidneys but not in normal kidneys. Reverse transcription-polymerase chain reaction (RT-PCR) as well as Northern blotting demonstrate that CD44 kidney mRNA levels are increased in nephritic MRL-lpr mice compared with normal mice. To further characterize the tubular CD44 expression, we examined cultured TEC (primary cultures and SV40-transformed TEC lines C1 and MCT). TEC constitutively express abundant cell surface CD44 that is modestly up-regulated in response to 18 hours stimulation with TNF-alpha (100 ng/ml), IFN-gamma (100 U/ml) and IL-1 (100 ng/ml). Northern analysis of TEC mRNA reveals a constitutive CD44 mRNA transcript at 3 kb. Stimulation with IFN-gamma or TNF-alpha for six hours markedly up-regulates CD44 mRNA expression in these cells. We conclude that mononuclear infiltration with CD44 positive cells and cytokine-induced up-regulation of CD44 by renal TEC is a prominent feature of MRL-lpr lupus nephritis. The contribution of CD44 induction on TEC to the pathogenesis of the autoimmune nephritic process in MRL-lpr remains to be determined.
Benz
P S
PS
Physiological Institute, University of Zürich, Switzerland.
Fan
X
X
Wüthrich
R P
RP
D000818:Animals; D002460:Cell Line; D004848:Epithelium / Q000737:chemistry; D018960:Hyaluronan Receptors / Q000032:analysis*; D007371:Interferon-gamma / Q000494:pharmacology; D007684:Kidney Tubules / Q000737:chemistry*; D008181:Lupus Nephritis / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D018960:Hyaluronan Receptors; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma