Pattern Recognition by Pentraxins

Abstract

Pentraxins are a family of evolutionarily conserved pattern-recognition proteins that are made up of five identical subunits. Based on the primary structure of the subunit, the pentraxins are divided into two groups: short pentraxins and long pentraxins. C-reactive protein (CRP) and serum amyloid P-component (SAP) are the two short pentraxins. The prototype protein of the long pentraxin group is pentraxin 3 (PTX3). CRP and SAP are produced primarily in the liver while PTX3 is produced in a variety of tissues during inflammation. The main functions of short pentraxins are to recognize a variety of pathogenic agents and then to either eliminate them or neutralize their harmful effects by utilizing the complement pathways and macrophages in the host. CRP binds to modified low-density lipoproteins, bacterial polysaccharides, apoptotic cells, and nuclear materials. By virtue of these recognition functions, CRP participates in the resolution of cardiovascular, infectious, and autoimmune diseases. SAP recognizes carbohydrates, nuclear substances, and amyloid fibrils and thus participates in the resolution of infectious diseases, autoimmunity, and amyloidosis. PTX3 interacts with several ligands, including growth factors, extracellular matrix component and selected pathogens, playing a role in complement activation and facilitating pathogen recognition by phagocytes. In addition, data in gene-targeted mice show that PTX3 is essential in female fertility, participating in the assembly of the cumulus oophorus extra-cellular matrix. PTX3 is therefore a nonredundant component of the humoral arm of innate immunity as well as a tuner of inflammation. Thus, in conjunction with the other components of innate immunity, the pentraxins use their pattern-recognition property for the benefit of the host.

C‐Reactive Protein Identifies Low‐Risk Metabolically Healthy Obese Persons: The European Prospective Investigation of Cancer–Norfolk Prospective Population Study

“…C‐reactive protein (CRP) is an acute‐phase protein of the family of the pentraxins and is widely used in clinical settings to monitor chronic and acute inflammatory conditions 1. The positive association between CRP levels and the risk of future coronary heart disease (CHD) has been studied extensively 2, 3.…”

C-reactive protein, immunoglobulin G and complement co-localize in renal immune deposits of proliferative lupus nephritis

“…These evolutionarily highly conserved pattern recognition molecules (PRMs) are pivotal components of the innate immune system and are of great interest in relation to the pathogenesis of lupus. The affinity of CRP and other pentraxins for cell nuclear antigens, their ability to activate the classical complement pathway and their affinity for Fc-receptors is thought provoking in relation to deficient 'waste disposal' and ANA formation in SLE, where a CRP response is often low or absent despite raised interleukin 6 in disease flares [11][12][13]. Homozygous deficiency of C1q and C1r/C1s is associated with a very high risk to develop lupus (≥90%), whereas heterozygous genetic deficiency of C1 components appears not to be associated with decreased serum levels of C1q or an increased risk of developing SLE [14].…”

Human Galectin 3 Binding Protein Interacts with Recombinant Adeno-Associated Virus Type 6

“…By using a multidisciplinary approach involving proteomics, binding assays, electron microscopy (EM), and in vivo studies, we demonstrated that rAAV-6 interacted specifically with C-reactive protein (CRP) in mice and galectin 3 binding protein (G3BP) in humans and dogs. Interestingly, CRP belongs to the short pentraxins, whose main functions are to recognize a variety of pathogenic agents (2), and G3BP contains a scavenger receptor cysteine-rich (SRCR) domain, which plays an important role in uptake and clearance of weakened components, such as modified host molecules and apoptotic cells (26,37). We found that in human serum human G3BP (hu-G3BP) was able to aggregate and precipitate rAAV-6.…”