Membrane-associated C-reactive protein on rat liver macrophages is synthesized within the macrophages, expressed as Neo–C-reactive protein and bound through a C-reactive protein-specific membrane receptor

Abstract

We could recently show that rat liver macrophages (Kupffer cells) express a membrane-bound form of C-reactive protein on their surface. Because it is removed by washing the cells in buffers containing Ca(++)-chelators, membrane-bound C-reactive protein is a peripheral protein rather than an integral part of the Kupffer cell membrane. This Kupffer cell membrane-bound C-reactive protein is identical to the galactose-specific particle receptor previously characterized. We now present evidence that Kupffer cells do not acquire soluble serum C-reactive protein but synthesize their own membrane-bound C-reactive protein. By RNA-RNA in situ hybridization, it was found that hepatocytes are not the only sort of liver cells synthesizing C-reactive protein, but C-reactive protein-specific mRNA is present also in Kupffer cells. During acute-phase response C-reactive protein mRNA is found in increased amounts within liver macrophages too. Furthermore, by labeling experiments with antisera against native, pentameric soluble serum C-reactive protein and monoclonal antibodies against a neoepitope present on C-reactive protein subunits only, we could establish that the membrane-bound C-reactive protein expressed on the liver macrophage is not the pentameric molecule of soluble serum C-reactive protein, but rather consists of C-reactive protein subunits. Finally, we present evidence that liver macrophages contain a binding protein in their plasma membrane, with an apparent molecular weight of 59 to 61kD, specific for C-reactive protein and similar to the one previously isolated from macrophage cell lines.

CD4 T Cell Tolerance to Human C-reactive Protein, an Inducible Serum Protein, Is Mediated by Medullary Thymic Epithelium

“…In view of previous reports on a membrane-bound form of CRP being expressed by subsets of macrophages in human and rat (13, 37, 38), we first assessed the influence of hCRP transgenic hemopoietic cells on the development of Dep cells. When lethally irradiated B6 mice were reconstituted with bone marrow cells from Dep × hCRP mice, thereby generating animals in which only hemopoietic cells carried the hCRP transgene, no deletion of the Dep TCR was observed.…”

“…Several particular features would predict strong immunogenicity of APPs upon induction: ( a ) the presence of very high serum levels (up to 2 mg/ml); ( b ) as part of the innate immune response, APPs accumulate at the site of infection and antigen processing; and ( c ) the uptake of APPs by professional APCs may be facilitated by specific surface receptors (12, 13). How is tolerance maintained under such conditions?…”

Prognostic role of serum C-reactive protein in esophageal cancer: a systematic review and meta-analysis

“…CRP is synthesized mainly by hepatocytes. 12 , 13 Production of CRP by hepatocytes is induced mainly by IL-6, although other cytokines, such as tumor necrosis factor α (TNFα), transforming growth factor β (TGFβ), and IL-1, can also synthesize this protein. 35 , 36 It has been reported that IL-6 is able to contribute to the cancer growth and progression.…”

“… 9 – 11 CRP is synthesized mainly by hepatocytes as a part of the SIR. 12 , 13 CRP is a representative acute-phase reactant and is the most widely used systemic biomarker of inflammation. 14 , 15 …”

C-Reactive Protein: A Family of Proteins to Regulate Cardiovascular Function

“…A growing body of evidence indicates extrahepatic synthesis of CRP. CRP messenger RNA and/or protein were detected in monocytedepleted peripheral-blood lymphocytes, 58,59 peripheral-blood mononuclear cells, 60 rat Kupffer cells, 61 macrophages, 13,62 islet cells of the pancreas, 63 neurons, 64 adipose tissue, 65 endothelial and smooth muscle cells, 17,18 kidneys, 66 and epithelial cells of the respiratory tract. 14 Most of the described CRP proteins synthesized extrahepatically express poor solubility (ie, the protein is not secreted, is either expressed intracellularly or bound to the cell membrane) and express mCRP ("neo-CRP") antigenicity.…”