TY - JOUR
T1 - The kidney as a second site of human C-reactive protein formation in vivo
AU - Jabs, Wolfram J.
AU - Lögering, Birgit A.
AU - Gerke, Peter
AU - Kreft, Burkhard
AU - Wolber, Eva Maria
AU - Klinger, Matthias Heinrich Friedrich
AU - Fricke, Lutz
AU - Steinhoff, Jürgen
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2003/1/1
Y1 - 2003/1/1
N2 - C-reactive protein (CRP) is the main acute phase reactant in humans. Its production is pre-sumably restricted to the liver but extrahepatic expression by inflamed tissue has not been studied in detail. By real-time PCR and immunohistochemistry we here show that renal cortical tubular epithelial cells (TEC) express CRP mRNA and protein within 6 h after stimulation with conditioned medium (CM) or IL-6, but not IL-1α or TNF-α. Western blot analysis with monoclonal anti-CRP antibody that recognizes native CRP revealed protein secretion into supernatants of CM-stimulated TEC cultures. While hepatoma-derived Hep3B cells could be induced similarly, peripheral blood mononuclear cells could not. CRP mRNA transcripts were observed in nephrectomized renal allografts with severe acute rejection but not with chronic allograft nephropathy (CAN). Of 19 needle biopsies of acutely rejecting kidney transplants, 15 demonstrated CRP mRNA production with the relative expression levels increasing with the severity of rejection. On the other hand, none of 7 graft biopsies with acute tubular necrosis (ATN) or CAN showed CRP mRNA expression. By using monoclonal anti-CRP antibody, cortical tubules as well as glomerular cells were shown to locally express CRP in rejecting, but not in ATN kidneys. We conclude that inflamed kidneys represent a so far unknown site of CRP formation in vivo. These data shed new light on the acute phase reaction not merely representing a systemic inflammatory pathway but probably being part of the local immune response.
AB - C-reactive protein (CRP) is the main acute phase reactant in humans. Its production is pre-sumably restricted to the liver but extrahepatic expression by inflamed tissue has not been studied in detail. By real-time PCR and immunohistochemistry we here show that renal cortical tubular epithelial cells (TEC) express CRP mRNA and protein within 6 h after stimulation with conditioned medium (CM) or IL-6, but not IL-1α or TNF-α. Western blot analysis with monoclonal anti-CRP antibody that recognizes native CRP revealed protein secretion into supernatants of CM-stimulated TEC cultures. While hepatoma-derived Hep3B cells could be induced similarly, peripheral blood mononuclear cells could not. CRP mRNA transcripts were observed in nephrectomized renal allografts with severe acute rejection but not with chronic allograft nephropathy (CAN). Of 19 needle biopsies of acutely rejecting kidney transplants, 15 demonstrated CRP mRNA production with the relative expression levels increasing with the severity of rejection. On the other hand, none of 7 graft biopsies with acute tubular necrosis (ATN) or CAN showed CRP mRNA expression. By using monoclonal anti-CRP antibody, cortical tubules as well as glomerular cells were shown to locally express CRP in rejecting, but not in ATN kidneys. We conclude that inflamed kidneys represent a so far unknown site of CRP formation in vivo. These data shed new light on the acute phase reaction not merely representing a systemic inflammatory pathway but probably being part of the local immune response.
UR - http://www.scopus.com/inward/record.url?scp=0037258396&partnerID=8YFLogxK
U2 - 10.1002/immu.200390018
DO - 10.1002/immu.200390018
M3 - Scientific review articles
C2 - 12594844
AN - SCOPUS:0037258396
SN - 0014-2980
VL - 33
SP - 152
EP - 161
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 1
ER -