TY - JOUR
T1 - Expression of SDF-1/CXCR4 in injured human kidneys
AU - Lotan, Danny
AU - Sheinberg, Natalia
AU - Kopolovic, Jury
AU - Dekel, Benjamin
N1 - Funding Information:
This study was partially supported by grants from the Israel Scientific Foundation Physician-Scientist Grant Award, Sheba Career Development Award, and Moriss Kahn Career Development Award (BD). We thank Anat Shlosberg for her technical assistance.
PY - 2008/1
Y1 - 2008/1
N2 - The chemokine SDF-1α 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-1α. To further investigate a possible role of SDF-1α 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-1α, CXCR4, and CD45, a pan-hematopoietic marker. Irrespective of the diagnosis, intense SDF-1α 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-1α in these sites. In all investigated renopathologic conditions, CD45+ leukocyte recruitment to the kidney seems not to be driven by SDF-1α/CXCR4 interaction. A contribution of SDF-1α for influx of CXCR4+ cells in the vicinity of arcuate vessels is suggested only in human ATN.
AB - The chemokine SDF-1α 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-1α. To further investigate a possible role of SDF-1α 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-1α, CXCR4, and CD45, a pan-hematopoietic marker. Irrespective of the diagnosis, intense SDF-1α 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-1α in these sites. In all investigated renopathologic conditions, CD45+ leukocyte recruitment to the kidney seems not to be driven by SDF-1α/CXCR4 interaction. A contribution of SDF-1α for influx of CXCR4+ cells in the vicinity of arcuate vessels is suggested only in human ATN.
KW - CD45
KW - Ischemic injury
KW - Renal inflammation
KW - SDF-1α/CXCR4
KW - Stem cells
UR - http://www.scopus.com/inward/record.url?scp=37049022440&partnerID=8YFLogxK
U2 - 10.1007/s00467-007-0648-2
DO - 10.1007/s00467-007-0648-2
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AN - SCOPUS:37049022440
SN - 0931-041X
VL - 23
SP - 71
EP - 77
JO - Pediatric Nephrology
JF - Pediatric Nephrology
IS - 1
ER -