Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\27053688
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Am+J+Physiol+Renal+Physiol
2016 ; 311
(1
): F176-81
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
C-reactive protein exacerbates renal ischemia-reperfusion injury: are
myeloid-derived suppressor cells to blame?
#MMPMID27053688
Pegues MA
; McWilliams IL
; Szalai AJ
Am J Physiol Renal Physiol
2016[Jul]; 311
(1
): F176-81
PMID27053688
show ga
Myeloid-derived suppressor cells (MDSCs) are a CD11b(+)Gr1(+) population in mice
that can be separated into granulocytic (g-MDSC) and monocytic (m-MDSC) subtypes
based on their expression of Ly6G and Ly6C. Both MDSC subtypes are potent
suppressors of T cell immunity, and their contribution has been investigated in a
plethora of diseases including renal cancer, renal transplant, and chronic kidney
disease. Whether MDSCs contribute to the pathogenesis of acute kidney injury
(AKI) remains unknown. Herein, using human C-reactive protein (CRP) transgenic
(CRPtg) and CRP-deficient mice (CRP(-/-)) subjected to bilateral renal
ischemia-reperfusion injury (IRI), we confirm our earlier finding that CRP
exacerbates renal IRI and show for the first time that this effect is accompanied
in CRPtg mice by a shift in the balance of kidney-infiltrating MDSCs toward a
suppressive Ly6G(+)Ly6C(low) g-MDSC subtype. In CRPtg mice, direct depletion of
g-MDSCs (using an anti-Gr1 monoclonal antibody) reduced the albuminuria caused by
renal IRI, confirming they play a deleterious role. Remarkably, treatment of
CRPtg mice with an antisense oligonucleotide that specifically blocks the human
CRP acute-phase response also led to a reduction in renal g-MDSC numbers and
improved albuminuria after renal IRI. Our study in CRPtg mice provides new
evidence that MDSCs participate in the pathogenesis of renal IRI and shows that
their pharmacological depletion is beneficial. If ongoing investigations confirm
that CRP is an endogenous regulator of MDSCs in CRPtg mice, and if this action is
recapitulated in humans, then targeting CRP or/and MDSCs might offer a new
approach for the treatment of AKI.
free
free
free
