Control of the acute phase response. Demonstration of C-reactive protein synthesis and secretion by hepatocytes during acute inflammation in the rabbit.

Abstract

To determine the cell of origin of C-reactive protein (CRP) and to cast light on the mechanisms leading to the acute phase response, we used an immunoenzymatic technique to visualize this protein in livers from rabbits at intervals after intramuscular injection of turpentine. CRP was detected only in hepatocytes. 8 h after turpentine injection, CRP was demonstrated in occasional periportal hepatocytes. With time, larger numbers of positive cells were detected successively in perilobular, midlobular, and centrilobular areas. On electron microscopy, CRP was detected in rough endoplasmic reticulum (RER), smooth endoplasmic reticulum (SER), and Golgi apparatus (GA). When colchicine was administered to inhibit cellular secretion of CRP, intensity of reaction and number of CRP-containing hepatocytes were substantially greater than without colchicine, but the sequence of intralobular distribution was similar. At peak serum response 38 h after turpentine injection, CRP could be demonstrated in most hepatocytes. Electron microscopic studies showed accumulation of CRP on membranes and lumina of RER, SER, GA, and in cytoplasmic vacuoles. These findings indicate that CRP is produced by progressively increasing numbers of hepatocytes after inflammatory stimulus and suggest that a mediator, acting initially in portal zones, is responsible for recruitment of cells to CRP production.

Evaluation of the use of serum C-reactive protein concentration to predict outcome in puppies infected with canine parvovirus

“…16 In dogs, CRP is primarily produced in the liver by de novo synthesis and released into the bloodstream following stimulation by proinflammatory cytokines. 16,18 The extent of changes in circulating CRP concentrations during the course of disease seems to reflect underlying disease progression and inflammatory activity.…”

Statins and nitric oxide reduce C-reactive protein production while inflammatory conditions persist

“…Any role of CRP in the pathogenesis of atherosclerosis is not certain, although elevated serum CRP is considered as a predictor of cardiovascular diseases (Libby and Ridker, 2004). CRP is primarily produced by hepatocytes (Kushner and Feldmann, 1978) and can be experimentally induced in human hepatoma Hep3B cells by treatment with proinflammatory cytokines IL-6 and IL-1 (Ganapathi et al, 1991). In these cells, induction of CRP expression by (IL-6 + IL-1 ) is further enhanced by dexamethasone (Dex) (Ganapathi et al, 1991).…”

Induction of hepatic synthesis of serum amyloid A protein and actin.

“…the serum are increased as much as 1000-fold by infection, inflammation, or malignant neoplasia (1,2). One of these acute-phase proteins is C-reactive protein, which is believed to play a role in defense against infection.…”

“…An attractive hypothesis to explain the rapid increase of SAAL concentration after LPS administration is induction of de novo biosynthesis by hepatocytes, followed shortly by release into the serum, as seen with C-reactive protein (2). ["Induction" is used to refer to specific stimulation ofthe relative rate of synthesis of a particular protein without implying an increase in synthesis of its mRNA (7)].…”