Efficient renal recruitment of macrophages and T cells in mice lacking the duffy antigen/receptor for chemokines
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Efficient renal recruitment of macrophages and T cells in mice lacking the duffy antigen/receptor for chemokines. / Vielhauer, Volker; Allam, Ramanjaneyulu; Lindenmeyer, Maja T; Cohen, Clemens D; Draganovici, Dan; Mandelbaum, Jana; Eltrich, Nuru; Nelson, Peter J; Anders, Hans-Joachim; Pruenster, Monika; Rot, Antal; Schlöndorff, Detlef; Segerer, Stephan.
In: AM J PATHOL, Vol. 175, No. 1, 07.2009, p. 119-31.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Efficient renal recruitment of macrophages and T cells in mice lacking the duffy antigen/receptor for chemokines
AU - Vielhauer, Volker
AU - Allam, Ramanjaneyulu
AU - Lindenmeyer, Maja T
AU - Cohen, Clemens D
AU - Draganovici, Dan
AU - Mandelbaum, Jana
AU - Eltrich, Nuru
AU - Nelson, Peter J
AU - Anders, Hans-Joachim
AU - Pruenster, Monika
AU - Rot, Antal
AU - Schlöndorff, Detlef
AU - Segerer, Stephan
PY - 2009/7
Y1 - 2009/7
N2 - 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.
AB - 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.
KW - Animals
KW - Chemokines
KW - Chemotaxis, Leukocyte
KW - Duffy Blood-Group System
KW - Enzyme-Linked Immunosorbent Assay
KW - Fibrosis
KW - Flow Cytometry
KW - Glomerulonephritis
KW - Image Processing, Computer-Assisted
KW - Immunoglobulin G
KW - Immunohistochemistry
KW - Macrophages
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Receptors, Cell Surface
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - T-Lymphocytes
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.2353/ajpath.2009.080590
DO - 10.2353/ajpath.2009.080590
M3 - SCORING: Journal article
C2 - 19498001
VL - 175
SP - 119
EP - 131
JO - AM J PATHOL
JF - AM J PATHOL
SN - 0002-9440
IS - 1
ER -