Endogenous and exogenous pentraxin-3 limits postischemic acute and chronic kidney injury
| Autor: | Bernd Uhl, Regina Gröbmayr, Heni Eka Susanti, Christoph Römmele, Onkar P. Kulkarni, Shijun Wang, Hans-Joachim Anders, Fritz Krombach, Cecilia Garlanda, Hermann Josef Gröne, Christoph A. Reichel, Alberto Mantovani, Maciej Lech |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Pathology Time Factors Kidney Mice 0302 clinical medicine Fibrosis Leukocytes Cells Cultured Mice Knockout 0303 health sciences biology Acute kidney injury PTX3 Acute Kidney Injury Recombinant Proteins 3. Good health P-Selectin C-Reactive Protein medicine.anatomical_structure Neutrophil Infiltration Nephrology Reperfusion Injury Female Tumor necrosis factor alpha Inflammation Mediators medicine.medical_specialty Nerve Tissue Proteins Injections 03 medical and health sciences medicine Animals Renal Insufficiency Chronic 030304 developmental biology Interleukin-6 Tumor Necrosis Factor-alpha business.industry Macrophages C-reactive protein Transendothelial and Transepithelial Migration Kidney Tubular Necrosis Acute medicine.disease Mice Inbred C57BL Disease Models Animal Immunology biology.protein Atrophy business Reperfusion injury 030215 immunology Kidney disease |
| Zdroj: | Kidney International |
| ISSN: | 0085-2538 |
| DOI: | 10.1038/ki.2012.463 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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