Studies of Acute Phase Protein

Kushner, Irving; Kaplan, Melvin H.

doi:10.1084/jem.114.6.961

Cited by 133 publications

(53 citation statements)

References 18 publications

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“…The demonstration that colchicine-treated animals showed many more and stronger staining positive cells than did untreated animals may partially explain previous difficulties encountered in demonstrating CRP-producing cells in liver employing immunofluorescent methods (18). In those studies, in which colchicine was not administered, the rapid secretion rate in most cells would have greatly diminished the likelihood of detecting positive cells.…”

Section: Discussionmentioning

confidence: 99%

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

Kushner¹,

Feldmann²

1978

The Journal of Experimental Medicine

198

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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.

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Section: Discussionmentioning

confidence: 99%

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

Kushner¹,

Feldmann²

1978

The Journal of Experimental Medicine

198

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“…Thus, we propose that the generation of oxidized PtC on the cell surface, and͞or an alteration in the lipid milieu of the membrane in which PtC are found (as noted below) lead to exposure of PC moieties, which could mediate CRP binding. CRP has been reported to bind to cell membranes, as well as to intracellular components such as chromatin-containing H1 and small nuclear ribonucleoprotein (30)(31)(32). Initial evidence for the binding specificity of CRP to cells was provided by immunohistochemical studies demonstrating that CRP was associated with cell membranes of damaged and necrotic cells, but not normal cells, at sites of inflammation and tissue necrosis (30).…”

Section: Crp Frequently Colocalizes With the Eo6 Epitope In Human Athmentioning

confidence: 99%

“…CRP has been reported to bind to cell membranes, as well as to intracellular components such as chromatin-containing H1 and small nuclear ribonucleoprotein (30)(31)(32). Initial evidence for the binding specificity of CRP to cells was provided by immunohistochemical studies demonstrating that CRP was associated with cell membranes of damaged and necrotic cells, but not normal cells, at sites of inflammation and tissue necrosis (30). Recently, Gershov et al (2) reported that CRP binds to the surface membrane of apoptotic cells and subsequently promotes clearance, but the ligand mediating such binding was not characterized.…”

Section: Crp Frequently Colocalizes With the Eo6 Epitope In Human Athmentioning

confidence: 99%

C-reactive protein binds to both oxidized LDL and apoptotic cells through recognition of a common ligand: Phosphorylcholine of oxidized phospholipids

Chang

Binder²,

Torzewski³

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

450

354

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C-reactive protein (CRP) is an acute-phase protein that binds specifically to phosphorylcholine (PC) as a component of microbial capsular polysaccharide and participates in the innate immune response against microorganisms. CRP elevation also is a major risk factor for cardiovascular disease. We previously demonstrated that EO6, an antioxidized LDL autoantibody, was a T15 clono-specific anti-PC antibody and specifically binds to PC on oxidized phosphatidylcholine (PtC) but not on native PtC. Similarly, EO6 binds apoptotic cells but not viable cells. In addition, such oxidized phospholipids are recognized by macrophage scavenger receptors, implying that these innate immune responses participate in the clearance because of their proinflammatory properties. We now report that CRP binds to oxidized LDL (OxLDL) and oxidized PtC (OxPtC), but does not bind to native, nonoxidized LDL nor to nonoxidized PtC, and its binding is mediated through the recognition of a PC moiety. Reciprocally, CRP binds to PC, which can be competed for by OxLDL and OxPtC but not by native LDL, nonoxidized PtC, or by oxidized phospholipids without the PC headgroup. CRP also binds to apoptotic cells, and this binding is competed for by OxLDL, OxPtC, and PC. These data suggest that CRP binds OxLDL and apoptotic cells by recognition of a PC moiety that becomes accessible as a result of oxidation of PtC molecule. We propose that, analogous to EO6 and scavenger receptors, CRP is a part of the innate immune response to oxidized PC-bearing phospholipids within OxLDL and on the plasma membranes of apoptotic cells.atherosclerosis ͉ innate immunity ͉ scavenger receptors ͉ autoantibody EO6

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“…gets deposited at sites of tissue damage and inflammation (12,13). Two types of molecular contacts are known for the binding of CRP to its ligands, one that requires calcium ions (Ca 2ϩ ) and another that does not require Ca 2ϩ and instead is inhibited by Ca 2ϩ (2).…”

mentioning

confidence: 99%

Interaction of Calcium-bound C-reactive Protein with Fibronectin Is Controlled by pH

Suresh

Singh

Agrawal

2004

Journal of Biological Chemistry

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Studies of Acute Phase Protein

Abstract: PLATES 90 TO 92

Cited by 133 publications

References 18 publications

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

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

C-reactive protein binds to both oxidized LDL and apoptotic cells through recognition of a common ligand: Phosphorylcholine of oxidized phospholipids

Interaction of Calcium-bound C-reactive Protein with Fibronectin Is Controlled by pH

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