Can von Willebrand factor, platelet-endothelial cell adhesion molecule-1 and thrombomodulin be used as alternative markers of endothelial cell injury in human glomerulonephritis?
OBJECTIVE
There is growing evidence that endothelial cells (EC) are active participants of an inflammatory process in glomeruli.


METHODS
We compared the glomerular expression of three EC-coupled molecules, i.e. platelet-endothelial cell adhesion molecule-1 (PECAM-1 or CD31), von Willebrand factor (vWF) and thrombomodulin (TM) in 60 patients with glomerulonephritis (GN) and five normal kidneys (NK). The alkaline phosphatase anti-alkaline phosphatase method was used to examine the expression of these proteins in the biopsy specimens.


RESULTS
In NK, the expression of CD31 and vWF comprised the whole glomerular network. In contrast, the expression of TM was much lower and localized mainly to EC at the vascular pole and adjacent areas. In GN, the glomerular staining for CD31 and vWF was significantly reduced. A fall in the expression of both these EC antigens was more pronounced in proliferative forms of GN (PGN) than in non-proliferative GN (NPGN) (CD31: NPGN vs. PGN, p < 0.02; vWF: NPGN vs. PGN, p < 0.05). In addition, a linear relationship between the expression of CD31 and vWF was found in GN (r = 0.8, p < 0.001). Conversely to CD31 and vWF, a marked increase in glomerular reactivity for TM was observed in all the patients with GN (GN: 2.12 +/- 0.32, NK: 0.95 +/- 0.05, p < 0.02). However, the highest expression of TM was found in membranoproliferative GN and lupus GN.


CONCLUSIONS
Our results suggest that CD31 and vWF may be used as markers of glomerular EC loss during GN, whereas TM staining seems to reflect EC activation in response to circulating and/or released in situ procoagulant factors.
Niemir
Z I
ZI
Laboratory for Molecular Nephrology, Department of Nephrology, Transplantology and Internal Diseases, Karol Marcinkowski University of Medical Sciences, Poznań, Poland. zniemir@usoms.poznan.pl
Kubiak
A
A
Olejniczak
P
P
Nowak
A
A
Czekalski
S
S
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D004730:Endothelium, Vascular / Q000293:injuries*; D005260:Female; D015870:Gene Expression; D005921:Glomerulonephritis / Q000097:blood* / Q000473:pathology; D006801:Humans; D007678:Kidney Glomerulus / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000097:blood*; D018180:Thrombomodulin / Q000097:blood*; D014841:von Willebrand Factor / Q000378:metabolism*
D015415:Biomarkers; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018180:Thrombomodulin; D014841:von Willebrand Factor