title: Efficient renal recruitment of macrophages and T cells in mice lacking the duffy antigen/receptor for chemokines.
abstract: 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.
authors.affiliation: Medizinische Poliklinik, Campus Innenstadt, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Vielhauer
authors.forename: Ramanjaneyulu
authors.initials: R
authors.lastname: Allam
authors.forename: Maja T
authors.initials: MT
authors.lastname: Lindenmeyer
authors.forename: Clemens D
authors.initials: CD
authors.lastname: Cohen
authors.forename: Dan
authors.initials: D
authors.lastname: Draganovici
authors.forename: Jana
authors.initials: J
authors.lastname: Mandelbaum
authors.forename: Nuru
authors.initials: N
authors.lastname: Eltrich
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Nelson
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Anders
authors.forename: Monika
authors.initials: M
authors.lastname: Pruenster
authors.forename: Antal
authors.initials: A
authors.lastname: Rot
authors.forename: Detlef
authors.initials: D
authors.lastname: Schlöndorff
authors.forename: Stephan
authors.initials: S
authors.lastname: Segerer
mesh_terms: 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
chemical_list: D018925:Chemokines; D004375:Duffy Blood-Group System; D007074:Immunoglobulin G; D011956:Receptors, Cell Surface; C483025:Ackr1 protein mouse