The kidney as a second site of human C‐reactive protein formation in vivo

Abstract

C-reactive protein (CRP) is the main acute phase reactant in humans. Its production is presumably 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-1 § or TNF- § . 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.

Elevated pentraxin-3 levels are related to blood pressure levels in hypertensive patients: an observational study

“…It is also proclaimed that high HDL cholesterol levels or low LDL/HDL ratio adversely affects the release of PTX3 from adipose tissues, while high LDL cholesterol levels are correlated with high PTX3 levels (28,29). It is also emphasized that this fact could be one of the secrets behind the development of atherosclerosis (28).…”

Inflammatory Cytokines Stimulated C-Reactive Protein Production by Human Coronary Artery Smooth Muscle Cells

“…[5][6][7][8][9] Two studies have shown that both epithelial cells of the respiratory tract and renal epithelium produce CRP. 14,18 Moreover, neuronal cells also Figure 1. Effect of cytokine and LPS treatment on CRP protein production in HCASMCs.…”

“…13 In addition, renal cortical tubular epithelial cells were shown to produce CRP after inflammatory stimuli. 14 Interestingly, CRP has also been found in human atherosclerotic plaques, 15 which could be the result of indirect deposit from circulating cells or direct production by cells in the arterial wall. We show that human coronary artery smooth muscle cells (HCASMCs), but not human umbilical vein endothelial cells (HUVECs), can synthesize CRP after stimulation by inflammatory cytokines.…”

C-reactive protein, immunoglobulin G and complement co-localize in renal immune deposits of proliferative lupus nephritis

“…However, since anti-CRP antibodies in SLE are not directed against the circulating pentameric form of CRP but rather to CRP monomers, a more likely pathogenic potential of circulating anti-CRP would be to target tissue-bound monomeric CRP (mCRP) [22]. Such mCRP has been detected in vessels, skeletal muscle, liver and in tissue of chronic renal disease, possibly with extrahepatically produced CRP [29][30][31][32]. The well-known fact that pentameric CRP activates the classical complement pathway, has also been reported to account for mCRP [33][34][35].…”