Efficient renal recruitment of macrophages and T cells in mice lacking the duffy antigen/receptor for chemokines.
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.
Vielhauer
Volker
V
Medizinische Poliklinik, Campus Innenstadt, Ludwig-Maximilians-University Munich, Munich, Germany.
Allam
Ramanjaneyulu
R
Lindenmeyer
Maja T
MT
Cohen
Clemens D
CD
Draganovici
Dan
D
Mandelbaum
Jana
J
Eltrich
Nuru
N
Nelson
Peter J
PJ
Anders
Hans-Joachim
HJ
Pruenster
Monika
M
Rot
Antal
A
Schlöndorff
Detlef
D
Segerer
Stephan
S
D000818:Animals; D051379:Mice; D018925:Chemokines / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004375:Duffy Blood-Group System / Q000235:genetics / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005355:Fibrosis; D005434:Flow Cytometry; D005921:Glomerulonephritis / Q000276:immunology / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D007074:Immunoglobulin G / Q000097:blood; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology
D018925:Chemokines; D004375:Duffy Blood-Group System; D007074:Immunoglobulin G; D011956:Receptors, Cell Surface; C483025:Ackr1 protein mouse