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Structure and Function of Humanc-Reactive Protein
Published in Andrzej Mackiewicz, Irving Kushner, Heinz Baumann, Acute Phase Proteins, 2020
Alok Agrawal, John M. Kilpatrick, John E. Volanakis
C-reactive protein (CRP) is the most characteristic human acute phase protein, since its plasma concentration rises by several hundredfold within 24 to 48 h from tissue injury.1 These high levels persist for the duration of the acute phase response, returning to the normal low concentrations with restoration of tissue structure and function. Based on its structure and calcium-dependent binding specificities, CRP is classified as a pentraxin.2 Members of the pentraxin family of proteins exhibit a remarkable conservation of structure and binding reactivities. All pentraxins consist of single polypeptide chain subunits, arranged in pentagonal or, rarely, hexagonal cyclic symmetry and discernible by electron microscopy. All pentraxins bind Ca2+ ions, which are necessary for the expression of ligand-binding activity. In vertebrates, there are two main branches of pentraxins. CRP-like members bind phosphocholine (PCh) and SAP (serum amyloid P)-like members bind carbohydrate moieties. Not all pentraxins are acute phase proteins. For example, in humans, CRP is an acute phase protein and SAP is not, while in mice the reverse is true.3
Inflammation, Inflammatory Markers, and Cardiovascular Risk
Published in P. K. Shah, Risk Factors in Coronary Artery Disease, 2006
Among the various markers, considerable attention has been devoted to circulating levels of CRP as a risk indicator. CRP is an acute phase protein with a plasma half life of 19 hours, named for its ability to precipitate the C-polysaccharide of Pneumococcus. It is a member of the pentraxin family of calcium dependant ligand-binding plasma proteins involved in the innate immune system produced almost exclusively by liver in response to IL-6 after tissue injury, infection, or other inflammatory stimuli. The human CRP molecule consists of five identical non-glycosylated polypeptide chains each containing 206 amino acids (29). The CRP levels in blood can be measured accurately and reproducibly down to very low levels using recently developed high sensitivity assays. It is a stable molecule with a long half life and does not exhibit circadian variation. Subjects in the general population tend to have stable CRP levels characteristic for each individual except for occasional increases associated with minor or subclinical infections, trauma, or inflammation. Twin studies show a highly significant genetic basis for CRP levels which is independent of age and body mass index. The levels of CRP may also be regulated by genetic variations (30–32).
Serum Amyloid P Component in Mink *
Published in Gilles Grateau, Robert A. Kyle, Martha Skinner, Amyloid and Amyloidosis, 2004
Lone A. Omtvedt, Tale N. Wien, Theresa Myran, Knut Sletten, Gunnar Husby
Isolation and characterisation of serum pentraxins; Proteins were purified from mink serum by affinity chromatography, either using PE coupled ECH-sepharose 4B (Amersham Biosciences) or immobilised PC-gel (Pierce Biotechnology) (2). The purity of the sample was analysed by SDS-PAGE and N-terminal sequencing. Alkylated and non-alkylated SAP purified from control serum, was digested with trypsin, with staphylococcal V8 protease or with endoproteinase ASP-N (Roch) according to the manufacturer (7–8). Chemical fragmentation with CNBr was performed both on filter and in solution (9). Proteins and peptides were analysed by automatic Edman degradation and by mass spectrometry.
Immunological mechanisms underlying sterile inflammation in the pathogenesis of atherosclerosis: potential sites for intervention
Published in Expert Review of Clinical Immunology, 2021
Roland Truong, Finosh G. Thankam, Devendra K. Agrawal
Pentraxin 3 (PTX3) is an acute phase protein that belongs to a superfamily of multimeric proteins including short and long pentraxins. PTX3 is a PRR and plays a critical role in innate immunity. Levels of PTX3 are elevated in elderly hypertensive patients and clinical data have suggested PTX3 to be a valid biomarker in atherosclerosis as it is directly correlated with the severity of carotid stenosis and in patients with acute coronary syndromes. PTX3 increases tissue factor, an upstream initiator of the coagulation cascade [60]. Surprisingly, there are conflicting reports concerning PTX3 in cardiovascular disease. In a study, lesions in the aorta were increased in PTX3−/- and ApoE−/- mice that were fed atherogenic diet for 16 weeks. Mice lacking PTX3 demonstrated a higher inflammatory profile suggesting an atheroprotective effect of PTX3 [61].
Plasma pentraxin 3 is associated with progression of radiographic joint damage, but not carotid atherosclerosis, in female rheumatoid arthritis patients: 3-year prospective study
Published in Modern Rheumatology, 2020
Yu Funakubo Asanuma, Yoshimi Aizaki, Hisashi Noma, Kazuhiro Yokota, Mayumi Matsuda, Noritsune Kozu, Yoshitake Takebayashi, Hiroshi Nakatani, Tomoko Hasunuma, Shinichi Kawai, Toshihide Mimura
Pentraxin 3 has an important role in inflammation, innate immunity, remodeling of the extracellular matrix, and development of atherosclerosis. Pentraxin 3 is a long pentraxin, which belongs to the pentraxin protein family and shares the C-terminal pentraxin domain with short pentraxins such as C-reactive protein (CRP). While CRP is produced by the liver in response to interleukin-6 stimulation [8], pentraxin 3 is produced in response to interleukin-1 and tumor necrosis factor-alpha by various cells, including macrophages, dendritic cells, polymorphonuclear leukocytes, fibroblasts, endothelial cells, and smooth muscle cells [9]. Thus, the plasma pentraxin 3 level is recognized as a marker of inflammation. Recent studies have indicated that pentraxin 3 has a role in bone homeostasis. It was shown to promote osteoclastogenesis in vitro by increasing human osteoblast receptor activator of nuclear factor kappa-B ligand (RANKL) production [10]. On the other hand, pentraxin 3-deficient mice show impaired bone formation during bone remodeling and regeneration following fracture, suggesting that pentraxin 3 is involved in bone formation [11].
Brief Commentary on the Article “Diagnostic Value of Plasma Pentraxin-3 in Acute Appendicitis”
Published in Journal of Investigative Surgery, 2019
Pentraxin-3(PTX-3) is a secretory protein classified as a long pentraxin member of the pentraxin family. This protein is structurally found to be related to CRP, but distinct in that pentraxin-3 subunits are approximately twice as large as CRP subunits (46 kDa molecular mass vs. 23 kDa). Hence, the smaller CRP could be lost from the vascular compartment due to leakage, while the larger pentraxin-3 could be protected from such a loss. Pentraxin-3 is produced by a wide variety of cells including macrophages and endothelial cells, in response to primary inflammatory stimuli like Tumour Necrosis Factor-alpha (TNF), interleukin-1(IL-1), and microbial products like lipo-polysaccharides and lipo-arabinomannans. Plasma levels of pentraxin-3 are usually measured using sandwich enzyme-linked immuno-sorbent assay (ELISA) technique and are expressed as nanograms per milliliter (ng/ml), the normal levels in healthy persons being 2 ng/ml.