CCR2-dependent Gr1high monocytes promote kidney injury in shiga toxin-induced hemolytic uremic syndrome in mice
2018
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
monocyticcompartment and in
CCR2-binding chemokines have been observed. However, the specific contribution of
CCR2-dependent Gr1high
monocytesis unknown. To investigate the impact of these
monocytesduring HUS, we injected a combination of LPS and
Shiga toxininto mice. We observed an impaired kidney function and elevated levels of the
CCR2-binding chemokine
CCL2after
Shiga toxin/LPS- injection, thus suggesting Gr1high
monocyteinfiltration into the kidney. Indeed, the number of Gr1high
monocyteswas 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 cortexand this damage coincided with the detection of Gr1high
monocytesin the
renal cortex. Lack of Gr1high
monocytesin
Ccr2-deficient animals reduced
neutrophil gelatinase-associated lipocalinand
blood urea nitrogenlevels. Moreover, the survival of
Ccr2-deficient animals was significantly improved. Conclusively, this study demonstrates that
CCR2-dependent Gr1high
monocytescontribute to the kidney injury during HUS and targeting these cells is beneficial during this disease. This article is protected by copyright. All rights reserved
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