CCR2-dependent Gr1hⁱgh monocytes promote kidney injury in shiga toxin-induced hemolytic uremic syndrome in mice
| Autor: | Nicolas Beziere, Alexandra Brenzel, Anthony Squire, Daniel R. Engel, Bernd J. Pichler, Walter Ehrlichmann, Faikah Gueler, Judith-Mira Pohl, Julia K. Volke, Stephanie Thiebes, Kerstin Fuchs |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
CCR2 Chemokine Kidney biology Monocyte Immunology Medizin Renal function Shiga toxin CCL2 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Integrin alpha M biology.protein medicine Immunology and Allergy 030215 immunology |
| Popis: | The hemolytic uremic syndrome (HUS) is a life-threatening disease of the kidney that is induced by shiga toxin-producing E.coli. Major changes in the monocytic compartment and in CCR2-binding chemokines have been observed. However, the specific contribution of CCR2-dependent Gr1high monocytes is unknown. To investigate the impact of these monocytes during HUS, we injected a combination of LPS and shiga toxin into mice. We observed an impaired kidney function and elevated levels of the CCR2-binding chemokine CCL2 after shiga toxin/LPS- injection, thus suggesting Gr1high monocyte infiltration into the kidney. Indeed, the number of Gr1high monocytes was strongly increased one day after HUS induction. Moreover, these cells expressed high levels of CD11b suggesting activation after tissue entry. Non-invasive PET-MR imaging revealed kidney injury mainly in the kidney cortex and this damage coincided with the detection of Gr1high monocytes. Lack of Gr1high monocytes in Ccr2-deficient animals reduced neutrophil gelatinase-associated lipocalin and blood urea nitrogen levels. Moreover, the survival of Ccr2-deficient animals was significantly improved. Conclusively, this study demonstrates that CCR2-dependent Gr1high monocytes contribute to the kidney injury during HUS and targeting these cells is beneficial during this disease. |
| Databáze: | OpenAIRE |
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