NK cells do not mediate renal injury in murine adriamycin nephropathy.
In adriamycin nephropathy (AN), a model of chronic proteinuric renal injury, the absence of functional B and T cells with residual natural killer (NK) cells, and macrophages in severe combined immunodeficient (SCID) mice results in more severe disease than in immunocompetent mice. We have recently shown expression of the stimulatory NK cell molecule NKG2D and its ligand RAE-1 in the adriamycin (ADR) kidney. Therefore, we sought to determine the role of NK cells in AN. We used anti-asialo GM1 NK cell depletion in immunocompetent BALB/c mice with AN, and also compared AN in immunodeficient SCID mice and immunodeficient nonobese diabetic (NOD)-SCID mice (that have impaired NK cell function). The number of NK cells was increased in AN in BALB/c mice compared with normal controls. NK cell depletion or reduction of NK function in NOD-SCID mice did not affect the severity of disease. In both wild type and immunodeficient models, ADR upregulated RAE-1 in the kidney. High levels of Class I major histocompatibility complex molecules were found in both models of AN. In conclusion, NK cells do not play a significant role in AN.
Centre for Transplantation and Renal Research, The University of Sydney at Westmead Millenium Institute, Sydney, Australia. guoping_zheng@wmi.usyd.edu.au
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Zheng
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Zheng
Y
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Wang
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Wu
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Kairaitis
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Zhang
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YC
Tay
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Y
Wang
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Alexander
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Harris
D000818:Animals; D004317:Doxorubicin / Q000633:toxicity*; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007668:Kidney / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D007677:Kidney Function Tests; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D055655:NK Cell Lectin-Like Receptor Subfamily K; D016133:Polymerase Chain Reaction; D011507:Proteinuria / Q000209:etiology; D011971:Receptors, Immunologic / Q000235:genetics; D055607:Receptors, Natural Killer Cell
D015395:Histocompatibility Antigens Class I; C527086:Klrk1 protein, mouse; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D004317:Doxorubicin