Pentraxins and Fc Receptor-Mediated Immune Responses.

C-reactive protein (CRP) is a member of the pentraxin family of proteins. These proteins are highly conserved over the course of evolution being present as far back as 250 million years ago. Mammalian pentraxins are characterized by the presence of five identical non-covalently linked subunits.

Pentraxins and IgA share a binding hot-spot on FcαRI.

The pentraxins, C-reactive protein (CRP), and serum amyloid P component (SAP) have previously been shown to function as innate opsonins through interactions with Fcγ receptors. The molecular details of these interactions were elucidated by the crystal structure of SAP in complex with FcγRIIA. More recently, pentraxins were shown to bind and activate FcαRI (CD89), the receptor for IgA.

Pentraxins: structure, function, and role in inflammation.

The pentraxins are an ancient family of proteins with a unique architecture found as far back in evolution as the Horseshoe crab. In humans the two members of this family are C-reactive protein and serum amyloid P. Pentraxins are defined by their sequence homology, their pentameric structure and their calcium-dependent binding to their ligands.

C-reactive protein inhibits plasmacytoid dendritic cell interferon responses to autoantibody immune complexes.

Objective: C-reactive protein (CRP) is a serum pattern recognition molecule that binds to apoptotic cells and nucleoprotein autoantigens and Fcγ receptors (FcγR). In systemic lupus erythematosus (SLE), immune complexes (ICs) containing nucleoprotein autoantigens activate plasmacytoid dendritic cells (PDCs) to produce type I interferon (IFN), which contributes to disease pathogenesis. Autoantibody ICs are taken up by PDCs through FcγR type IIa into endosomes, where the nucleic acid components activate Toll-like receptor 7 (TLR-7) or TLR-9.

Transforming growth factor-β, macrophage colony-stimulating factor and C-reactive protein levels correlate with CD14(high)CD16+ monocyte induction and activation in trauma patients.

Severe injury remains a leading cause of death and morbidity in patients under 40, with the number of annual trauma-related deaths approaching 160,000 in the United States. Patients who survive the initial trauma and post-traumatic resuscitation are at risk for immune dysregulation, which contributes to late mortality and accounts for approximately 20% of deaths after traumatic injury. This post-traumatic immunosuppressed state has been attributed to over-expression of anti-inflammatory mediators in an effort to restore host homeostasis.

Pentraxins and Fc receptors.

Pentraxins are innate pattern recognition molecules whose major function is to bind microbial pathogens or cellular debris during infection and inflammation and, by doing so, contribute to the clearance of necrotic cells as well as pathogens through complement activations. Fc receptors are the cellular mediators of antibody functions. Although conceptually separated, both pentraxins and antibodies are important factors in controlling acute and chronic inflammation and infections.

Recognition and functional activation of the human IgA receptor (FcalphaRI) by C-reactive protein.

C-reactive protein (CRP) is an important biomarker for inflammatory diseases. However, its role in inflammation beyond complement-mediated pathogen clearance remains poorly defined. We identified the major IgA receptor, FcαRI, as a ligand for pentraxins.

Pentraxins (CRP, SAP) in the process of complement activation and clearance of apoptotic bodies through Fcγ receptors.

Purpose Of Review: Ischemia/reperfusion injury and organ allograft rejection both entail excessive cell and tissue destruction. A number of innate immune proteins, including the pentraxins, participate in the removal of this potentially inflammatory and autoimmunogenic material. The classical pentraxins, C-reactive protein (CRP) and serum amyloid P component (SAP) are serum opsonins, which bind to damaged membranes and nuclear autoantigens.

Macrophages activated by C-reactive protein through Fc gamma RI transfer suppression of immune thrombocytopenia.

C-reactive protein (CRP) is an acute-phase protein with therapeutic activity in mouse models of systemic lupus erythematosus and other inflammatory and autoimmune diseases. To determine the mechanism by which CRP suppresses immune complex disease, an adoptive transfer system was developed in a model of immune thrombocytopenic purpura (ITP). Injection of 200 microg of CRP 24 h before induction of ITP markedly decreased thrombocytopenia induced by anti-CD41.

Structural recognition and functional activation of FcgammaR by innate pentraxins.

Pentraxins are a family of ancient innate immune mediators conserved throughout evolution. The classical pentraxins include serum amyloid P component (SAP) and C-reactive protein, which are two of the acute-phase proteins synthesized in response to infection. Both recognize microbial pathogens and activate the classical complement pathway through C1q (refs 3 and 4).

C-reactive protein at the interface between innate immunity and inflammation.

C-reactive protein (CRP), the prototypic acute-phase protein, increases rapidly in response to infection and inflammation. Although CRP was thought to be a passive, nonspecific marker of inflammation, recent studies indicate that CRP plays a key role in the innate immune system by recognizing pathogens and altered self determinants. Activation of complement and interaction with Fcgamma receptors by CRP provides a link between the innate and adaptive immune systems.

C-reactive protein enhances immunity to Streptococcus pneumoniae by targeting uptake to Fc gamma R on dendritic cells.

C-reactive protein (CRP) is an acute phase reactant with roles in innate host defense, clearance of damaged cells, and regulation of the inflammatory response. These activities of CRP depend on ligand recognition, complement activation, and binding to FcgammaR. CRP binds to phosphocholine in the Streptococcus pneumoniae cell wall and provides innate defense against pneumococcal infection.

C-reactive protein-mediated suppression of nephrotoxic nephritis: role of macrophages, complement, and Fcgamma receptors.

C-reactive protein (CRP) is a member of the pentraxin family of proteins and an acute phase reactant. CRP modulates the response to inflammatory stimuli including LPS and C5a. We recently demonstrated that CRP prevents and reverses proteinuria in accelerated nephrotoxic nephritis (NTN).

The biological effects of CRP are not attributable to endotoxin contamination: evidence from TLR4 knockdown human aortic endothelial cells.

C-reactive protein (CRP) is the prototypic marker of inflammation and a strong predictor of cardiovascular events in humans. There are questions regarding the validity of the biological effects reported for CRP, in spite of adherence to rigorous control measures minimizing endotoxin [lipopolysaccharide (LPS)] contamination in these in vitro studies. In this study, we addressed the key question of endotoxin contamination in CRP preparations using Toll-like receptor 4 (TLR4) knockdown endothelial cells.

C-reactive protein increases cytokine responses to Streptococcus pneumoniae through interactions with Fc gamma receptors.

Streptococcus pneumoniae is the most common organism responsible for community acquired pneumonia and meningitis. In pneumococcal pneumonia, a strong local inflammatory cytokine response reduces the frequency of bacteremia and increases survival. The initiation of this cytokine response by innate recognition of bacterial cell wall components through TLR has been described, but the role of soluble innate mediators has received limited attention.

Prevention and reversal of nephritis in MRL/lpr mice with a single injection of C-reactive protein.

Objective: C-reactive protein (CRP) is an acute-phase serum protein with binding reactivity to nuclear autoantigens and immunomodulatory function. The MRL/lpr mouse is an important model of human systemic lupus erythematosus (SLE). These mice develop high-titer anti-DNA antibodies and immune complex-mediated nephritis and exhibit progressive lymphadenopathy.

C-reactive protein: ligands, receptors and role in inflammation.

C-reactive protein (CRP) is the prototypical acute phase serum protein, rising rapidly in response to inflammation. CRP binds to phosphocholine (PC) and related molecules on microorganisms and plays an important role in host defense. However, a more important role may be the binding of CRP to PC in damaged membranes.

Analysis of binding sites in human C-reactive protein for Fc{gamma}RI, Fc{gamma}RIIA, and C1q by site-directed mutagenesis.

Human C-reactive protein (CRP) is a classical, acute phase serum protein synthesized by the liver in response to infection, inflammation, or trauma. CRP binds to microbial antigens and damaged cells, opsonizes particles for phagocytosis and regulates the inflammatory response by the induction of cytokine synthesis. These activities of CRP depend on its ability to activate complement and to bind to Fcgamma receptors (FcgammaR).

Binding and internalization of C-reactive protein by Fcgamma receptors on human aortic endothelial cells mediates biological effects.

Objective: In addition to being a cardiovascular risk marker, recent studies support a role for CRP in atherothrombosis. Several investigators have reported that CRP binds to Fcgamma receptors on leukocytes. The aim of the study is to determine the processing of CRP by human aortic endothelial cells (HAECs).

Studies of serum C-reactive protein in systemic lupus erythematosus.

Objective: To examine the relationship of serum C-reactive protein (CRP) levels to other indicators of disease activity during the course of systemic lupus erythematosus (SLE).

Methods: In 124 patients serum CRP was measured retrospectively by ELISA and in some instances by radial immunodiffusion. Serum CRP levels were compared to laboratory, clinical, and radiographic assessments of disease activity.

Reversal of ongoing proteinuria in autoimmune mice by treatment with C-reactive protein.

Objective: To examine the ability of injection of C-reactive protein (CRP) to treat systemic lupus erythematosus (SLE) in the (NZB x NZW)F(1) (NZB/NZW) mouse and to use a nephrotoxic nephritis (NTN) model to further examine the mechanism of this activity.

Methods: NZB/NZW mice were given a single injection of 200 mug of CRP prior to disease onset or after the onset of high-grade proteinuria. Mice were monitored weekly for proteinuria and monthly for anti-double-stranded DNA (anti-dsDNA) antibodies.

C-reactive protein: an activator of innate immunity and a modulator of adaptive immunity.

C-reactive protein (CRP) is an acute-phase serum protein and a member of the pentraxin protein family. Its host defense functions predate the adaptive immune system by millions of years. Our current understanding of CRP interactions with complement and with Fcgamma receptors (FcgammaR) have led to an increased appreciation of the regulatory role of CRP in inflammation and autoimmunity.

C-reactive protein mediates protection from lipopolysaccharide through interactions with Fc gamma R.

C-reactive protein (CRP) is a component of the acute phase response to infection, inflammation, and trauma. A major activity of acute phase proteins is to limit the inflammatory response. It has been demonstrated that CRP protects mice from lethal doses of LPS.

Serum amyloid P component and C-reactive protein opsonize apoptotic cells for phagocytosis through Fcgamma receptors.

Serum amyloid P component (SAP) and C-reactive protein (CRP) are opsonins that react with nuclear autoantigens targeted in systemic autoimmunity. CRP and SAP bind to apoptotic and necrotic cells, which are potential sources of these autoantigens. We have recently determined that the receptors for CRP on phagocytic cells are Fcgamma receptors.