Pentraxins (Pentaxins) are an evolutionary conserved family of proteins characterized by a pentraxin protein domain. They are a class of pattern recognition receptors.
Members of the Pentraxin Family
1. C-Reactive Protein:
CRP is a member of the pentraxin family of proteins which are molecules composed of 5 identical subunits arranged in a planar configuration. CRP is an acute phase protein that is found at dramatically increased levels in serum following injury, infection or inflammation. CRP was first described by Tillet and Francis (j. Exp. Med. 1930) who observed that sera from acutely ill patients precipitated with the C-polysaccharid of the cell wall of Streptococcus pneumonia. Other investigators subsequently identified the reactive serum factor as protein, hence the designation “C-reactive protein”. CRP binds phosphocholine residues on S. pneumoniae cell walls.
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, opsonized particles for phagocytosis and regulates the inflammatory response by the induction of cytokine synthesis. CRP thus exhibits multiple functional similarities to antibodies including activation of complement via the CP, binding to receptors on phagocytic cells, induction of cytokine synthesis and enhancement of phagocytosis. These functional similarities are expolained by the shared ability of CRP and IgG to interact with complement component C1q and with Fc? receptors (Fc?R) I and II. Bang (J. Bio. Chem, 280(26), 2005) have identified various amino acids with are critical for CRP binding to Fc?RI. Of interest, Du Clos have shown that CRP can downregualte inflammation through interaction with Fc? receptors in a mouse model for nephritis in SLE. Mice injected with CRP developed proteinuria later and survived longer than mice in control groups (Du Cos “Enhanced survival of NZBxNZWF1 female mice receiving a single injection of human CRP), FASEB 17(7): pC38, 2003).
The primary stimulus for CRP production is IL-6. Serum levels of CRP is disease usually correlate with levels of IL-6 in the blood. In SLE, CRP levels do not correlate with serum IL-6 suggesting an abnormal CRP response in patients with SLE.
Biological Activities: The biological activities of CRP are mediated by ligand binding and interaction with the Fc receptors for IgG (FcyR) in the case of phagocytic cells or activation of the complement system. These biological activities include recognizing and promoting the clearance of damaged cells, nuclear antigen and microbial pathogens. CRP binds to nuclear antigen that are the target of the autoantibodies of patients with SLE as well as to damaged membranes and microbial antigens. CRP binds to chromatin, histones, and small nuclear ribonucleoproteins (snRNPs) through a phosphocholine (PC)-inhibitable, calcium-dependent binding site.
CRP exhibits different biological activities under different conditions. These activities depend on ligand recognition, activation of complement and interactions with Fc gamma receptors (FcyR) I and II and perhaps FcyRIII. Although CRP may enhance inflammation and ligand clearance through complement activation, one of its most important functions appears to be the direct modulation of inflammation through interaction with FcyR. Depending on the level and type of FcyR expressed on cells at the site of CRP interaction, the outcome of CRP binding may be either pro- or anti-inflammatory. Under most conditions it is likely that CRP plays an anti-inflammatory and immunomodulatory role in acute inflammation and helps to clear damaged self and foreign materials from the circulation in a non-inflammatory and non-immunogenic manner.
2. Serum amyloid P component (SAP)
SAP is a member of the pentraxin family of proteins. These proteins are characterized by cyclic pentameric structure, calcium-dependent ligand binding, and frequent regulation as acute-phase serum proteins. SAP is the serum precursor of the P component of amyloid. It binds to a broad group of molecules including autantigens, through a pattern recognition binding site.