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Renal immune surveillance and dipeptidase-1 contribute to contrast-induced acute kidney injury.
Lau, Arthur; Chung, Hyunjae; Komada, Takanori; Platnich, Jaye M; Sandall, Christina F; Choudhury, Saurav Roy; Chun, Justin; Naumenko, Victor; Surewaard, Bas Gj; Nelson, Michelle C; Ulke-Lemée, Annegret; Beck, Paul L; Benediktsson, Hallgrimur; Jevnikar, Anthony M; Snelgrove, Sarah L; Hickey, Michael J; Senger, Donna L; James, Matthew T; Macdonald, Justin A; Kubes, Paul; Jenne, Craig N; Muruve, Daniel A.
Afiliação
  • Lau A; Department of Medicine.
  • Chung H; Snyder Institute for Chronic Diseases.
  • Komada T; Department of Medicine.
  • Platnich JM; Snyder Institute for Chronic Diseases.
  • Sandall CF; Department of Medicine.
  • Choudhury SR; Snyder Institute for Chronic Diseases.
  • Chun J; Department of Medicine.
  • Naumenko V; Snyder Institute for Chronic Diseases.
  • Surewaard BG; Department of Biochemistry and Molecular Biology.
  • Nelson MC; Libin Cardiovascular Institute of Alberta.
  • Ulke-Lemée A; Department of Oncology.
  • Beck PL; Arnie Charbonneau Cancer Institute.
  • Benediktsson H; Department of Medicine.
  • Jevnikar AM; Snyder Institute for Chronic Diseases.
  • Snelgrove SL; Snyder Institute for Chronic Diseases.
  • Hickey MJ; Department of Microbiology, Immunology, and Infectious Diseases, and.
  • Senger DL; Snyder Institute for Chronic Diseases.
  • James MT; Department of Microbiology, Immunology, and Infectious Diseases, and.
  • Macdonald JA; Department of Medicine.
  • Kubes P; Snyder Institute for Chronic Diseases.
  • Jenne CN; Department of Biochemistry and Molecular Biology.
  • Muruve DA; Libin Cardiovascular Institute of Alberta.
J Clin Invest ; 128(7): 2894-2913, 2018 07 02.
Article em En | MEDLINE | ID: mdl-29863495
ABSTRACT
Radiographic contrast agents cause acute kidney injury (AKI), yet the underlying pathogenesis is poorly understood. Nod-like receptor pyrin containing 3-deficient (Nlrp3-deficient) mice displayed reduced epithelial cell injury and inflammation in the kidney in a model of contrast-induced AKI (CI-AKI). Unexpectedly, contrast agents directly induced tubular epithelial cell death in vitro that was not dependent on Nlrp3. Rather, contrast agents activated the canonical Nlrp3 inflammasome in macrophages. Intravital microscopy revealed diatrizoate (DTA) uptake within minutes in perivascular CX3CR1+ resident phagocytes in the kidney. Following rapid filtration into the tubular luminal space, DTA was reabsorbed and concentrated in tubular epithelial cells via the brush border enzyme dipeptidase-1 in volume-depleted but not euvolemic mice. LysM-GFP+ macrophages recruited to the kidney interstitial space ingested contrast material transported from the urine via direct interactions with tubules. CI-AKI was dependent on resident renal phagocytes, IL-1, leukocyte recruitment, and dipeptidase-1. Levels of the inflammasome-related urinary biomarkers IL-18 and caspase-1 were increased immediately following contrast administration in patients undergoing coronary angiography, consistent with the acute renal effects observed in mice. Taken together, these data show that CI-AKI is a multistep process that involves immune surveillance by resident and infiltrating renal phagocytes, Nlrp3-dependent inflammation, and the tubular reabsorption of contrast via dipeptidase-1.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Meios de Contraste / Dipeptidases / Injúria Renal Aguda / Vigilância Imunológica / Rim Tipo de estudo: Screening_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Meios de Contraste / Dipeptidases / Injúria Renal Aguda / Vigilância Imunológica / Rim Tipo de estudo: Screening_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article