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At least 19 recordsLinked to original sources
PubMed1997

Neuronal pentraxin receptor, a novel putative integral membrane pentraxin that interacts with neuronal pentraxin 1 and 2 and taipoxin-associated calcium-binding protein 49.

We have identified the first putative integral membrane pentraxin and named it neuronal pentraxin receptor (NPR). NPR is enriched by affinity chromatography on columns of a snake venom toxin, taipoxin, and columns of the taipoxin-binding proteins neuronal pentraxin 1 (NP1), neuronal pentraxin 2 (NP2), and taipoxin-associated calcium-binding protein 49 (TCBP49). The predominant form of NPR contains an putative NH2-terminal transmembrane domain and all forms of NPR are glycosylated. NPR has 49 and 48% amino acid identity to NP1 and NP2, respectively, and NPR message is expressed in neuronal regions that express NP1 and NP2. We suggest that NPR, NP1, NP2, and TCBP49 are involved in a pathway responsible for the transport of taipoxin into synapses and that this may represent a novel neuronal uptake pathway involved in the clearance of synaptic debris.

Amino Acid Sequence↗
PubMed2005

Elevated plasma levels of the long pentraxin, pentraxin 3, in severe dengue virus infections.

C-reactive protein is one of the most widely used indicators of the response of acute-phase proteins. The measurement of C-reactive protein in dengue, however, is clinically not useful, because of marginally elevated levels and absent association with disease severity. The prototypic long pentraxin, pentraxin 3, is an acute phase protein that is structurally related but distinct from C-reactive protein which has proven to correlate with the severity of bacterial infection in critically ill patients. The potential involvement of pentraxin 3 in dengue and its aptitude to predict more severe disease or poor clinical outcome has not been studied previously. We therefore measured pentraxin 3 plasma levels in 44 dengue virus infected patients. Pentraxin 3 levels were strikingly higher when compared to C-reactive protein levels, with highest pentraxin 3 values observed in the first 7 days after the onset of symptoms. Median pentraxin 3 levels at admission and peak levels during follow up were higher in patients suffering from dengue shock syndrome (at admission: 119.3 ng/ml [interquartile range 61.8--188.7], peak values during follow up: 147.9 ng/ml [interquartile range 85.7--204.3]) compared to levels found in patients with dengue fever and dengue hemorrhagic fever (at admission: 59.0 ng/ml [interquartile range 28.6--100.3], P=0.040; peak values during follow up: 80.8 ng/ml [interquartile range 36.1--168.1], P=0.020). Our results indicate that pentraxin 3 seems to be a marker of infection better than C-reactive protein in dengue. The role of pentraxin 3 in the pathogenesis of dengue and its potential as an early prognostic indicator of disease severity needs further assessment.

C-Reactive Protein↗
PubMed1997

Multimer formation and ligand recognition by the long pentraxin PTX3. Similarities and differences with the short pentraxins C-reactive protein and serum amyloid P component.

PTX3 is a prototypic long pentraxin consisting of a C-terminal 203-amino acid pentraxin-like domain coupled with an N-terminal 178-amino acid unrelated portion. The present study was designed to characterize the structure and ligand binding properties of human PTX3, in comparison with the classical pentraxins C-reactive protein and serum amyloid P component. Sequencing of Chinese hamster ovary cell-expressed PTX3 revealed that the mature secreted protein starts at residue 18 (Glu). Lectin binding and treatment with N-glycosidase F showed that PTX3 is N-glycosylated, sugars accounting for 5 kDa of the monomer mass (45 kDa). Circular dichroism analysis indicated that the protein consists predominantly of beta-sheets with a minor alpha-helical component. While in gel filtration the protein is eluted with a molecular mass of congruent with900 kDa, gel electrophoresis using nondenaturing, nonreducing conditions revealed that PTX3 forms multimers predominantly of 440 kDa apparent molecular mass, corresponding to decamers, and that disulfide bonds are required for multimer formation. The ligand binding properties of PTX3 were then examined. As predicted based on modeling, inductive coupled plasma/atomic emission spectroscopy showed that PTX3 does not have coordinated Ca2+. Unlike the classical pentraxins CRP and SAP, PTX3 did not bind phosphoethanolamine, phosphocholine, or high pyruvate agarose. PTX3 in solution, bound to immobilized C1q, but not C1s, and, reciprocally, C1q bound to immobilized PTX3. Binding of PTX3 to C1q is specific and saturable with a Kd 7.4 x 10(-8) M as determined by solid phase binding assay. The Chinese hamster ovary cell-expressed pentraxin domain bound C1q when multimerized. Thus, as predicted on the basis of computer modeling, the prototypic long pentraxin PTX3 forms multimers, which differ from those formed by classical pentraxins in terms of protomer composition and requirement for disulfide bonds, and does not recognize CRP/SAP ligands. The capacity to bind C1q, mediated by the pentraxin domain, is consistent with the view that PTX3, produced in tissues by endothelial cells or macrophages in response to interleukin-1 and tumor necrosis factor, may act as a local regulator of innate immunity.

Animals↗
PubMed2000

Biochemical interactions of the neuronal pentraxins. Neuronal pentraxin (NP) receptor binds to taipoxin and taipoxin-associated calcium-binding protein 49 via NP1 and NP2.

Neuronal pentraxin 1 (NP1), neuronal pentraxin 2 (NP2), and neuronal pentraxin receptor (NPR) are members of a new family of proteins identified through interaction with a presynaptic snake venom toxin taipoxin. We have proposed that these three neuronal pentraxins represent a novel neuronal uptake pathway that may function during synapse formation and remodeling. We have investigated the mutual interactions of these proteins by characterizing their enrichment on taipoxin affinity columns; by expressing NP1, NP2, and NPR singly and together in Chinese hamster ovary cells; and by generating mice that fail to express NP1. NP1 and NP2 are secreted, exist as higher order multimers (probably pentamers), and interact with taipoxin and taipoxin-associated calcium-binding protein 49 (TCBP49). NPR is expressed on the cell membrane and does not bind taipoxin or TCBP49 by itself, but it can form heteropentamers with NP1 and NP2 that can be released from cell membranes. This is the first demonstration of heteromultimerization of pentraxins and release of a pentraxin complex by proteolysis. These processes are likely to directly effect the localization and function of neuronal pentraxins in neuronal uptake or synapse formation and remodeling.

Animals↗
PubMed2002

Complete cDNA sequence of SAP-like pentraxin from Limulus polyphemus: implications for pentraxin evolution.

The serum amyloid P component (SAP)-like pentraxin Limulus polyphemus SAP is a recently discovered, distinct pentraxin species, of known structure, which does not bind phosphocholine and whose N-terminal sequence has been shown to differ markedly from the highly conserved N terminus of all other known horseshoe crab pentraxins. The complete cDNA sequence of Limulus SAP, and the derived amino acid sequence, the first invertebrate SAP-like pentraxin sequence, have been determined. Two sequences were identified that differed only in the length of the 3' untranslated region. Limulus SAP is synthesised as a precursor protein of 234 amino acid residues, the first 17 residues encoding a signal peptide that is absent from the mature protein. Phylogenetic analysis clusters Limulus SAP pentraxin with the horseshoe crab C-reactive proteins (CRPs) rather than the mammalian SAPs, which are clustered with mammalian CRPs. The deduced amino acid sequence shares 22% identity with both human SAP and CRP, which are 51% identical, and 31-35% with horseshoe crab CRPs. These analyses indicate that gene duplication of CRP (or SAP), followed by sequence divergence and the evolution of CRP and/or SAP function, occurred independently along the chordate and arthropod evolutionary lines rather than in a common ancestor. They further indicate that the CRP/SAP gene duplication event in Limulus occurred before both the emergence of the Limulus CRP variants and the mammalian CRP/SAP gene duplication. Limulus SAP, which does not exhibit the CRP characteristic of calcium-dependent binding to phosphocholine, is established as a pentraxin species distinct from all other known horseshoe crab pentraxins that exist in many variant forms sharing a high level of sequence homology.

Amino Acid Sequence↗
PubMed2004

The prototypic tissue pentraxin PTX3, in contrast to the short pentraxin serum amyloid P, inhibits phagocytosis of late apoptotic neutrophils by macrophages.

OBJECTIVE: Phagocytosis of apoptotic cells can be facilitated by complement components and short pentraxins, such as serum amyloid P (SAP). In contrast, the long pentraxin PTX3 was shown to inhibit phagocytosis of apoptotic Jurkat cells by dendritic cells and to bind late apoptotic polymorphonuclear leukocytes (PMNs). Recently, levels of the pentraxin PTX3 were shown to parallel disease activity in small-vessel vasculitis, which is often characterized by leukocytoclasia, a persistence of leukocyte remnants in the vessel wall. We undertook this study to test our hypothesis that PTX3 inhibits phagocytosis of late apoptotic PMNs by macrophages, thereby leading to their accumulation in the vessel wall. METHODS: Macrophages were allowed to phagocytose late apoptotic or secondary necrotic PMNs that were incubated with or without PTX3 for 30 minutes prior to phagocytosis. Phagocytosis was allowed to occur in the presence of 30% normal human serum with or without SAP and with or without depletion of complement. To discriminate between an inhibitory effect of PTX3 on binding and the internalization of apoptotic PMNs into macrophages, internalization was blocked by cytochalasin B. RESULTS: SAP and complement were both necessary for effective in vitro phagocytosis. In contrast, PTX3 inhibited phagocytosis in a dose-dependent manner, from 11% inhibition at 6.25 microg/ml to almost complete inhibition at 100 microg/ml. Furthermore, PTX3 partly affected binding of apoptotic PMNs to macrophages. CONCLUSION: PTX3, in contrast to SAP and complement, inhibits phagocytosis of late apoptotic PMNs by monocyte-derived macrophages in a dose-dependent manner. Therefore, PTX3 can play a role in the development of leukocytoclasia by affecting the clearance of apoptotic PMNs, thereby inducing their accumulation in the vessel wall.

Apoptosis↗
PubMedDate not supplied

Isolation and partial characterization of a pentraxin-like protein with complement-fixing activity from snapper (Pagrus auratus, Sparidae) serum.

Pentraxin-like molecules have been isolated from a number of fish species. However, little is known about the function of these proteins in the teleosts. In this study we report the isolation and characterization of a pentraxin-like molecule from the serum of snapper (Pagrus auratus) that has the ability to activate complement. This pentraxin-like protein was isolated from serum by calcium-dependent binding to agarose. SDS-PAGE analysis demonstrated an oligomeric protein of approximately 200k Da consisting of non-covalently bound subunits of 26 and 23 kDa. Protein sequencing revealed significant (50%) sequence identity with pentraxins from both Atlantic salmon (S. salar) and rainbow trout (O. mykiss). However, polyclonal antibodies raised against snapper pentraxin did not recognise salmon or trout pentraxin in Western blot analysis. Following LPS injection, snapper pentraxin levels increased 2-fold before gradually returning to basal levels. Most significantly, the isolated pentraxin initiated complement-mediated lysis of ligand-coated sheep erythrocytes in a dose-dependent fashion. In view of the similarity between the known fish pentraxins, and their similarity to mammalian serum amyloid P-components we conclude that the isolated protein may be a snapper pentraxin homologue.

Amino Acid Sequence↗
PubMed2006

Elevated maternal levels of the long pentraxin 3 (PTX3) in preeclampsia and intrauterine growth restriction.

OBJECTIVE: The prototypic long pentraxin pentraxin 3 is a new candidate marker for inflammatory conditions reflecting the involvement of the vascular bed. Endothelial dysfunction is a prominent feature of preeclampsia as a result of excessive maternal systemic inflammation. We investigated pentraxin 3 levels in preeclampsia and intrauterine growth restriction, pregnancy conditions related to altered placentation. STUDY DESIGN: We cross-sectionally studied nonpregnant women (n = 20); normal pregnancies in the first (n = 8), second (n = 10), and third (n = 26) trimester of pregnancy; 20 pregnancies complicated by preeclampsia; and 16 pregnancies complicated by intrauterine growth restriction. Maternal plasma samples were analyzed and pentraxin 3 determined by enzyme-linked immunosorbent assay. Pattern and site of placental expression of pentraxin 3 were studied by immunohistochemistry. RESULTS: In normal pregnancies pentraxin 3 concentrations were significantly higher than nonpregnant women and did not change among the 3 trimesters. Significantly higher levels of pentraxin 3 were found in preeclampsia (median values 13.8 versus 2.2 ng/mL; P < .001), compared with normal pregnancies. Intrauterine growth restriction pregnancies showed intermediate levels between normal and preeclamptic patients, but this difference was not significant, compared with normal pregnancies (median values 3.9 versus 2.2 ng/mL). No significant difference of pentraxin 3 levels was found between mild and severe preeclampsia. CONCLUSION: Elevated maternal plasma levels of pentraxin 3 in preeclamptic versus normal pregnancies could represent a marker of altered endothelial function, typical of preeclampsia.

Adult↗
PubMed1995

Human neuronal pentraxin II (NPTX2): conservation, genomic structure, and chromosomal localization.

We have previously identified a novel rat neuronal member of the pentraxin family (neuronal pentraxin) that may mediate the uptake of synaptic material and the presynaptic snake venom toxin, taipoxin. Here we report human cDNA and genomic sequences of a second neuronal pentraxin. This pentraxin, which we propose to name neuronal pentraxin II (NPII; gene symbol NPTX2), shows 54% amino acid identity to rat neuronal pentraxin (NPI) with 69% identity over the carboxyl-terminal half of NPI and is 88% identical to a newly identified sperm acrosomal pentraxin p50/apexin. Northern blot analysis reveals that NPII message is present in brain, testis, pancreas, liver, heart, and skeletal muscle, so, unlike NPI, NPII is not exclusively localized to neurons. Like NPI, NPII has potential N-linked glycosylation sites. The human NPII gene is 11 kb in length, contains four introns, and is localized to chromosome 7q21.3-q22.1. These data demonstrate the existence of a family of pentraxin proteins that are expressed in the brain and other tissues and that may play important roles in the uptake of extracellular material.

Amino Acid Sequence↗
PubMed2006

The long pentraxin PTX3 in vascular pathology.

Pentraxins are a family of evolutionarily conserved multifunctional pattern-recognition proteins characterized by a cyclic multimeric structure. 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 in response to IL-6, while PTX3 is produced by a variety of tissues and cells and in particular by innate immunity cells in response to proinflammatory signals and Toll-like receptor (TLR) engagement. PTX3 interacts with several ligands, including growth factors, extracellular matrix components and selected pathogens, playing a role in complement activation and facilitating pathogen recognition by phagocytes, acting as a predecessor of antibodies. In addition, PTX3 is essential in female fertility by acting as a nodal point for the assembly of the cumulus oophorus hyaluronan-rich extracellular matrix. Thus, the prototypic long pentraxin PTX3 is a multifunctional soluble pattern recognition receptor acting as a non-redundant component of the humoral arm of innate immunity and involved in tuning inflammation, in matrix deposition and female fertility.

Animals↗
PubMedDate not supplied

Changes in serum concentration of a serum amyloid P-like pentraxin in Atlantic salmon, Salmo salar L., during infection and inflammation.

A serum amyloid P-like pentraxin has been isolated from Atlantic salmon. Salmo salar L., based on its calcium dependent binding to agarose. The subunits of approximately 37 kDa were all glycosylated and when covalently linked together formed a pentamer with disulphide bonds between all subunits. A specific rabbit antiserum raised against the pentameric form was used to follow changes in serum levels of the salmon pentraxin during infection with Aeromonas salar and inflammation induced by Escherichia coli LPS or killed A. salmonicida. The salmon pentraxin level in normal serum was in the range approximately 50-300 microg/ml. Unlike pentraxins from other species, the salmon pentraxin showed only moderate but significant increases or decreases in response to E. coli LPS or A. salmonicida infection, respectively. Although pentraxins and pentraxin-like proteins are evolutionary conserved, not all pentraxins are acute phase responders suggesting that their most ancestral function(s) are not related to acute phase induction.

Animals↗
PubMed2002

Non-redundant role of the long pentraxin PTX3 in anti-fungal innate immune response.

Pentraxins are a superfamily of conserved proteins that are characterized by a cyclic multimeric structure. The classical short pentraxins, C-reactive protein (CRP) and serum amyloid P component (SAP), are acute-phase proteins produced in the liver in response to inflammatory mediators. Short pentraxins regulate innate resistance to microbes and the scavenging of cellular debris and extracellular matrix components. In contrast, long pentraxins have an unrelated, long amino-terminal domain coupled to the carboxy-terminal pentraxin domain, and differ, with respect to short pentraxins, in their gene organization, chromosomal localization, cellular source, and in their stimuli-inducing and ligand-recognition ability. To investigate the in vivo function of the long pentraxin PTX3, we generated mice deficient in Ptx3 by homologous recombination. Ptx3-null mice were susceptible to invasive pulmonary aspergillosis. Ptx3 binds selected microbial agents, including conidia of Aspergillus fumigatus, and we found that susceptibility of Ptx3-null mice was associated with defective recognition of conidia by alveolar macrophages and dendritic cells, as well as inappropriate induction of an adaptive type 2 response. Thus, the long pentraxin Ptx3 is a secreted pattern-recognition receptor that has a non-redundant role in resistance to selected microbial agents, in particular to the opportunistic fungal pathogen Aspergillus fumigatus.

Animals↗
PubMed2006

[The role of long pentraxin 3, a new inflammatory mediator in inflammatory responses].

Pentraxin 3 (PTX3) is suggested to play important roles in the innate resistance against pathogens, regulation of inflammatory reactions, and clearance of apoptotic cells. PTX3 is the first long pentraxin identified. Long pentraxin shares a C-terminal pentraxin domain with the classical short pentraxin (C-reactive protein, serum amyloid P), but holds an unrelated N-terminal domain that is unique to the long pentraxin. While the short pentraxin is produced only in the liver, PTX3 is made by diverse types of cells, prominently endothelial cells and macrophage, in response to inflammatory signals. Unlike the short pentraxin, the expression of PTX3 in multiple types of tissue cells implies a mechanism for local amplification of innate resistance at the site of infection and inflammation. PTX3 plasma levels are very low in normal subjects but are rapidly increased by inflammatory conditions resulting from a wide range of diseased states, from infection to autoimmune and degenerative disorders. Critically ill patients show elevated circulating levels of PTX3 which are determined by the severity of the disease. Clinical evidence has demonstrated that the elevated PTX3 levels might be a useful early and sensitive marker for severely ill patients. Further studies will definitely be needed to deepen our understanding of PTX3.

Acute-Phase Proteins↗
PubMedDate not supplied

A comparative study of pentraxin-like proteins in different fish species.

Pentraxins are a family of pentameric serum proteins that have been conserved in evolution and share sequence homology, similar subunit assembly and the capacity for calcium-dependent ligand binding. The classical pentraxins are human C-reactive protein (CRP) and serum amyloid P component (SAP). The sequence homology and gene organization indicate that they arose from a gene duplication of an ancestral pentraxin gene. They are usually isolated based on their affinity for phosphorylcholine and agarose, respectively. We have used this method for isolation of pentraxin-like proteins from normal serum of Atlantic salmon (Salmo salar), common wolffish (Anarhichas lupus), cod (Gadus morhua) and halibut (Hippoglossus hippoglossus). Although pentraxin structures have not been verified, the isolated proteins all appear to be pentraxin-like based on their binding specificity, molecular weight of subunits, cross-reactivity with antibodies to human pentraxins and N-terminal amino acid sequences. However, with the described method only one pentraxin-like protein was detected in each of the fish species.

Amino Acid Sequence↗
PubMed1996

Long pentraxins: an emerging group of proteins with diverse functions.

The earliest described pentraxins, C reactive protein (CRP) and serum amyloid P component (SAP), are cytokine-inducible acute phase proteins implicated in innate immunity whose concentrations in the blood increase dramatically upon infection or trauma. The highly conserved family of pentraxins was thought to consist solely of approximately 25 kDa proteins. Recently, several distinct larger proteins have been identified in which only the C-terminal halves show characteristic features of the pentraxin family. One of the recently described "long" pentraxins (TSG-14/PTX3) is inducible by TNF or IL-1 and is produced during the acute phase response. Other newly identified long pentraxins are constitutively expressed proteins associated with sperm-egg fusion (apexin/p50), may function at the neuronal synapse (neuronal pentraxin I, NPI), or may serve yet other, unknown functions (NPII and XL-PXN1). Evidence obtained by molecular modeling and by direct physicochemical analysis suggests that TSG-14 protein retains some characteristic structural features of the pentraxins, including the formation of pentameric complexes.

Amino Acid Sequence↗
PubMed2001

Dynamic induction of the long pentraxin PTX3 in the CNS after limbic seizures: evidence for a protective role in seizure-induced neurodegeneration.

Pentraxin 3, a prototypic long pentraxin, is induced by proinflammatory signals in the brain. Inflammatory cytokines are rapidly induced in glia by epileptic activity. We show that pentraxin 3 immunoreactivity and mRNA are enhanced in the rat forebrain above undetectable control levels by limbic seizures with a dual pattern of induction. Within 6 h from seizure onset, pentraxin 3 immunoreactivity was increased in astrocytes. Eighteen to 48 h later, specific neuronal populations and leucocytes were strongly immunoreactive only in areas of neurodegeneration. This staining was abolished when neuronal cell loss, but not seizures, was prevented by blocking N-methyl-D-aspartate receptors. Pentraxin 3 -/- mice had a more widespread seizure-related neuronal damage in the forebrain than their wild-type littermates although both groups had similar epileptic activity. Our results provide evidence that pentraxin 3 is synthesized in brain after seizures and may exert a protective role in seizure-induced neurodegeneration.

2-Amino-5-phosphonovalerate↗
PubMed2005

[The role of pentraxin 3 in the inflammatory and immune response].

Pentraxin 3 is the first detected and so far the most important protein from the recently recognized group called the long pentraxins. The structure and function of PTX3 resembles in many aspects that of the short or classical pentraxins, i.e. C-reactive protein and the serum amyloid P component. There are, however, several important differences between the two groups of pentraxins that will be mentioned in more detail in the article. All of the above mentioned pentraxins take an acitve part in the first-line defense of the host against invading pathogenic microorganisms and in the clearance of the host's own apoptotic cells. The latter mechanism impedes the onset of destructive autoimmune reactions. A biologically relevant antipode of PTX3 is represented by TNFalpha. Physiologic course of the defense reactions depends on a closely co-ordinated activity of both peptides. In case of an unchecked or missing activity of either peptide, a disturbance in their mutual balance results in increased susceptibility of the host to conditionally pathogenic fungi or in increased damage to host's own tissues inflicted by the defense reactions. This review article deals with the physiopathologic importace of pentraxin 3 as has been gained on the basis of the most up-to-date information.

Acute-Phase Proteins↗
PubMed1993

Identification of a novel member of the pentraxin family in Xenopus laevis.

Pentraxins are a family of acute phase reactants. Two family members, C-reactive protein (CRP) and serum amyloid P component (SAP), are known in a range of mammalian species. CRP and SAP are both about 200 residues long, and arose from a gene duplication event, apparently before the divergence of the mammalian orders. To elucidate the origins of mammalian pentraxins, we have searched for pentraxin-coding genes in the amphibian Xenopus laevis. We have identified a gene determining a protein (XL-PXN1) which is about twice the size expected: the XL-PXN1 gene appears to be a fusion between regions encoding an amino-terminal peptide of unknown function and a carboxy-terminal pentraxin. The pentraxin domain is more divergent from CRP and SAP than they are from each other: it provides an outgroup for analysis of the evolution of mammalian pentraxins and confirms that putative CRP and SAP proteins partly characterized in non-vertebrate species cannot be true homologues of the mammalian proteins.

Acute-Phase Proteins↗