Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-19918
Vielhauer, V; Allam, R; Lindenmeyer, M T; Cohen, C D; Draganovici, D; Mandelbaum, J; Eltrich, N; Nelson, P J; Anders, H J; Pruenster, M; Rot, A; Schlöndorff, D; Segerer, S (2009). Efficient renal recruitment of macrophages and T cells in mice lacking the duffy antigen/receptor for chemokines. American Journal of Pathology:119-131.
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The Duffy antigen/receptor for chemokines (DARC) is a chemokine-binding protein that is expressed on erythrocytes and renal endothelial cells. DARC-mediated endothelial transcytosis of chemokines may facilitate the renal recruitment of macrophages and T cells, as has been suggested for neutrophils. We studied the role of Darc in two mouse models of prolonged renal inflammation, one that primarily involves the tubulointerstitium (unilateral ureteral obstruction), and one that requires an adaptive immune response that leads to glomerulonephritis (accelerated nephrotoxic nephritis). Renal expression of Darc and its ligands was increased in both models. Leukocytes effectively infiltrated obstructed kidneys in Darc-deficient mice with pronounced T-cell infiltration at early time points. Development of interstitial fibrosis was comparable in both genotypes. Nephrotoxic nephritis was inducible in Darc-deficient mice, with both an increased humoral immune response and functional impairment during the early phase of disease. Leukocytes efficiently infiltrated kidneys of Darc-deficient mice, with increased cell numbers at early but not late time points. Taken together, renal inflammation developed more rapidly in DARC-deficient mice, without affecting the extent of renal injury at later time points. Thus, genetic elimination of Darc in mice does not prevent the development of renal infiltrates and may even enhance such development during the early phases of interstitial and glomerular diseases in mouse models of prolonged renal inflammation.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Clinic for Nephrology|
04 Faculty of Medicine > Center for Integrative Human Physiology
04 Faculty of Medicine > Institute of Anatomy
04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Deposited On:||27 Jul 2009 14:42|
|Last Modified:||23 Nov 2012 14:14|
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