title: Endogenous and exogenous pentraxin-3 limits postischemic acute and chronic kidney injury.
abstract: Ischemia-reperfusion activates innate immunity and sterile inflammation, resulting in acute kidney injury. Since pentraxin 3 (PTX3) regulates multiple aspects of innate immunity and tissue inflammation, we tested whether PTX3 would be involved in renal ischemia-reperfusion injury. Renal pedicle clamping increased PTX3 serum levels, as well as PTX3 expression, inside the kidney but predominantly in CD45/CD11c(+) cells, a subpopulation of intrarenal mononuclear phagocytes. Lack of PTX3 aggravated postischemic acute kidney injury as evidenced by massive tubular necrosis, and TNF and IL-6 release, as well as massively increased neutrophil and macrophage infiltrates at 24 h. This was followed by tubular atrophy, interstitial fibrosis, and kidney shrinking 10 weeks later. In vivo microscopy uncovered increased leukocyte adhesion and transmigration in postischemic microvessels of Ptx3-deficient mice. Furthermore, injection of recombinant PTX3 up to 6 h after reperfusion prevented renal leukocyte recruitment and postischemic kidney injury. Thus, local PTX3 release from a subpopulation of intrarenal mononuclear phagocytes or delayed PTX3 treatment limits postischemic renal inflammation. Conversely, Ptx3 loss-of-function mutations predispose to postischemic acute kidney injury and subsequent chronic kidney disease.
authors: Division of Nephrology, Medizinische Klinik und Poliklinik IV, Campus Innenstadt, University of Munich-LMU, Munich, Germany.
authors: Maciej
authors: M
authors: Lech
authors: Christoph
authors: C
authors: Römmele
authors: Regina
authors: R
authors: Gröbmayr
authors: Heni
authors: H
authors: Eka Susanti
authors: Onkar P
authors: OP
authors: Kulkarni
authors: Shijun
authors: S
authors: Wang
authors: Hermann-Josef
authors: HJ
authors: Gröne
authors: Bernd
authors: B
authors: Uhl
authors: Christoph
authors: C
authors: Reichel
authors: Fritz
authors: F
authors: Krombach
authors: Cecilia
authors: C
authors: Garlanda
authors: Alberto
authors: A
authors: Mantovani
authors: Hans-Joachim
authors: HJ
authors: Anders
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D001284:Atrophy; D002097:C-Reactive Protein / Q000008:administration & dosage / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis; D018836:Inflammation Mediators / Q000378:metabolism; D007267:Injections; D015850:Interleukin-6 / Q000378:metabolism; D007668:Kidney / Q000098:blood supply* / Q000276:immunology* / Q000473:pathology; D007683:Kidney Tubular Necrosis, Acute / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D007962:Leukocytes / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000097:blood / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020556:Neutrophil Infiltration; D019007:P-Selectin / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D015427:Reperfusion Injury / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors; D057705:Transendothelial and Transepithelial Migration; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D018836:Inflammation Mediators; D015850:Interleukin-6; D009419:Nerve Tissue Proteins; D019007:P-Selectin; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D000099153:Pentraxins; C577686:interleukin-6, mouse