Expression of SDF-1/CXCR4 in injured human kidneys.
The chemokine SDF-1alpha is involved in migration, survival, and development of multiple cells, most notably of hematopoietic stem cells (HSC) expressing its ligand CXCR4. Recently, we have shown engraftment of human HSC in the ischemically injured murine kidney, presumably mediated by SDF-1alpha. To further investigate a possible role of SDF-1alpha in the recruitment of CXCR4(+) cells in human renal disease of varying etiologies, we immunostained human biopsies of immunoglobulin (Ig)A nephropathy, minimal-change nephrotic syndrome, focal segmental glomerulosclerosis, membranoproliferative glomerulonephritis, chronic pyelonephritis, and acute tubular necrosis (ATN) for SDF-1alpha, CXCR4, and CD45, a pan-hematopoietic marker. Irrespective of the diagnosis, intense SDF-1alpha immunoreactivity was localized to distal tubules and collecting ducts, whereas CXCR4 showed intense staining in both distal and proximal tubules. In addition, whereas varying degrees of CD45(+) cell infiltrates were observed in all biopsies, we found focal infiltrates of CXCR4(+) cells mostly localized to the corticomedullary junction only in ischemic ATN. This correlated with more extensive staining for SDF-1alpha in these sites. In all investigated renopathologic conditions, CD45+ leukocyte recruitment to the kidney seems not to be driven by SDF-1alpha/CXCR4 interaction. A contribution of SDF-1alpha for influx of CXCR4(+) cells in the vicinity of arcuate vessels is suggested only in human ATN.
Lotan
Danny
D
Department of Pediatric Nephrology, Sackler Faculty of Medicine, Tel Aviv University, Sheba Medical Center, Tel Hashomer 52621, Israel.
Sheinberg
Natalia
N
Kopolovic
Jury
J
Dekel
Benjamin
B
D000293:Adolescent; D000328:Adult; D000368:Aged; D054377:Chemokine CXCL12 / Q000032:analysis*; D002648:Child; D005260:Female; D006801:Humans; D007668:Kidney / Q000737:chemistry*; D007674:Kidney Diseases / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000032:analysis; D008297:Male; D008875:Middle Aged; D019718:Receptors, CXCR4 / Q000032:analysis*
C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4; D017493:Leukocyte Common Antigens