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This Article Full Text Full Text (PDF) All Versions of this Article: 293/2/F624    most recent 00398.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Rookmaaker, M. B. Articles by Rabelink, T. J. Search for Related Content PubMed PubMed Citation Articles by Rookmaaker, M. B. Articles by Rabelink, T. J.

Met-RANTES reduces endothelial progenitor cell homing to activated (glomerular) endothelium in vitro and in vivo

¹Department of Vascular Medicine, University Medical Center Utrecht, Utrecht; ²Department of Nephrology, Leiden University Medical Center, Leiden; Departments of ³Pathology and of ⁴Nephrology and Hypertension, University Medical Center Utrecht, Utrecht; and ⁵Department of Cellular and Molecular Pathology, German Cancer Research Center, Heidelberg, Germany

Submitted 7 October 2006 ; accepted in final form 31 May 2007

The chemokine RANTES (regulated upon activation normal T-cell expressed and secreted) is involved in the formation of an inflammatory infiltrate during glomerulonephritis. However, RANTES receptor inhibition, although reducing glomerular leukocyte infiltration, can also increase damage. We hypothesized that RANTES does not only promote the influx and activation of inflammatory leukocytes but also mediates glomerular microvascular repair by stimulating the homing of bone marrow (BM)-derived endothelial progenitor cells. To investigate the role of RANTES in the participation of BM-derived cells in glomerular vascular repair, we used a rat BM transplantation model in combination with reversible anti-Thy-1.1 glomerulonephritis. Twenty-four hours after the induction of glomerulonephritis, BM-transplanted rats were treated for 7 days with either the RANTES receptor antagonist Met-RANTES or saline. The participation of BM-derived endothelial cells in glomerular repair, glomerular monocyte infiltration, and proteinuria was evaluated at days 7 and 28. Furthermore, we used an in vitro perfusion chamber assay to study the role of RANTES receptors in shear-resistant adhesion of the CD34+ stem cells to activated endothelium under flow. In our reversible glomerulonephritis model, RANTES receptor inhibition specifically reduced the participation of BM-derived cells in glomerular vascular repair by more than 40% at day 7 without impairing monocyte influx. However, no obvious change in recovery from proteinuria or morphological damage was observed. Blockade of RANTES receptors on CD34+ cells in vitro partially inhibited platelet-enhanced, shear-resistant firm adhesion of the CD34+ cells to activated endothelium. In conclusion, our data suggest that RANTES is involved in the homing and participation of BM-derived endothelial cells in glomerular repair.

regulated upon activation normal T-cell expressed and secreted; glomerulonephritis; regeneration