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The Long Pentraxin PTX3 as a Link Between Innate Immunity, Tissue Remodeling, and Cancer.

ABSTRACT: The innate immune system comprises a cellular and a humoral arm. Humoral pattern recognition molecules include complement components, collectins, ficolins, and pentraxins. These molecules are involved in innate immune responses by recognizing microbial moieties and damaged tissues, activating complement, exerting opsonic activity and facilitating phagocytosis, and regulating inflammation. The long pentraxin PTX3 is a prototypic humoral pattern recognition molecule that, in addition to providing defense against infectious agents, plays several functions in tissue repair and regulation of cancer-related inflammation. Characterization of the PTX3 molecular structure and biochemical properties, and insights into its interactome and multiple roles in tissue damage and remodeling support the view that microbial and matrix recognition are evolutionarily conserved functions of humoral innate immunity molecules.

SUBMITTER: Doni A

PROVIDER: S-EPMC6459138 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The Long Pentraxin PTX3 as a Link Between Innate Immunity, Tissue Remodeling, and Cancer.

Doni Andrea A Stravalaci Matteo M Inforzato Antonio A Magrini Elena E Mantovani Alberto A Garlanda Cecilia C Bottazzi Barbara B

Frontiers in immunology 20190404

The innate immune system comprises a cellular and a humoral arm. Humoral pattern recognition molecules include complement components, collectins, ficolins, and pentraxins. These molecules are involved in innate immune responses by recognizing microbial moieties and damaged tissues, activating complement, exerting opsonic activity and facilitating phagocytosis, and regulating inflammation. The long pentraxin PTX3 is a prototypic humoral pattern recognition molecule that, in addition to providing ...[more]

PMID: 31019517

Similar Datasets

The "sweet" side of a long pentraxin: how glycosylation affects PTX3 functions in innate immunity and inflammation.

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| S-EPMC3539679 | biostudies-literature

The Long Pentraxin PTX3 as a Humoral Innate Immunity Functional Player and Biomarker of Infections and Sepsis.

Project description:The first line of defense in innate immunity is provided by cellular and humoral mediators. Pentraxins are a superfamily of phylogenetically conserved humoral mediators of innate immunity. PTX3, the first long pentraxin identified, is a soluble pattern recognition molecule rapidly produced by several cell types in response to primary pro-inflammatory signals and microbial recognition. PTX3 acts as an important mediator of innate immunity against pathogens of fungal, bacterial and viral origin, and as a regulator of inflammation, by modulating complement activation and cell extravasation, and facilitating pathogen recognition by myeloid cells. In sepsis, PTX3 plasma levels are associated with severity of the condition, patient survival, and response to therapy. In combination with other established biomarkers, PTX3 could improve stratification of sepsis patients and thus, complement the system of classification and monitoring of this disease.

| S-EPMC6473065 | biostudies-literature

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| S-EPMC7112810 | biostudies-literature

PTX3, a Humoral Pattern Recognition Molecule, in Innate Immunity, Tissue Repair, and Cancer.

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| S-EPMC5985957 | biostudies-literature

Long pentraxin PTX3 exacerbates pressure overload-induced left ventricular dysfunction.

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| S-EPMC3553104 | biostudies-literature

The Long Pentraxin PTX3 Controls <i>Klebsiella Pneumoniae</i> Severe Infection.

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| S-EPMC8173212 | biostudies-literature

A direct link between MITF, innate immunity, and hair graying.

Project description:Melanocyte stem cells (McSCs) and mouse models of hair graying serve as useful systems to uncover mechanisms involved in stem cell self-renewal and the maintenance of regenerating tissues. Interested in assessing genetic variants that influence McSC maintenance, we found previously that heterozygosity for the melanogenesis associated transcription factor, Mitf, exacerbates McSC differentiation and hair graying in mice that are predisposed for this phenotype. Based on transcriptome and molecular analyses of Mitfmi-vga9/+ mice, we report a novel role for MITF in the regulation of systemic innate immune gene expression. We also demonstrate that the viral mimic poly(I:C) is sufficient to expose genetic susceptibility to hair graying. These observations point to a critical suppressor of innate immunity, the consequences of innate immune dysregulation on pigmentation, both of which may have implications in the autoimmune, depigmenting disease, vitiligo.

| S-EPMC5933715 | biostudies-literature

The Long Pentraxin PTX3 Is of Major Importance Among Acute Phase Proteins in Chickens.

Project description:The expression level of acute phase proteins (APPs) mirrors the health status of an individual. In human medicine, C-reactive protein (CRP), and other members of the pentraxin family are of significant relevance for assessing disease severity and prognosis. In chickens, however, which represent the most common livestock species around the world, no such marker has yet gained general acceptance. The aim of this study was therefore, to characterize chicken pentraxin 3 (chPTX3) and to evaluate its applicability as a general marker for inflammatory conditions. The mammalian and chicken PTX3 proteins were predicted to be similar in sequence, domain organization and polymeric structure. Nevertheless, some characteristics like certain sequence sections, which have varied during the evolution of mammals, and species-specific glycosylation patterns, suggest distinct biological functions. ChPTX3 is constitutively expressed in various tissues but, interestingly, could not be found in splenic tissue samples without stimulation. However, upon treatment with lipopolysaccharide (LPS), PTX3 expression in chicken spleens increased to 95-fold within hours. A search for PTX3 reads in various publicly available RNA-seq data sets of chicken spleen and bursa of Fabricius also showed that PTX3 expression increases within days after experimental infection with viral and bacterial pathogens. An experimental infection with avian pathogenic E.coli and qPCR analysis of spleen samples further established a challenge dose-dependent significant up-regulation of chPTX3 in subclinically infected birds of up to over 150-fold as compared to untreated controls. Our results indicate the potential of chPTX3 as an APP marker to monitor inflammatory conditions in poultry flocks.

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Macrophage expression and prognostic significance of the long pentraxin PTX3 in COVID-19

Project description:PTX3 is an essential component of humoral innate immunity, involved in resistance to selected pathogens and in the regulation of inflammation1-3. The present study was designed to assess the presence and significance of PTX3 in COVID-194-7. RNA-seq analysis of peripheral blood mononuclear cells, single-cell bioinformatics analysis and immunohistochemistry of lung autopsy samples revealed that myelomonocytic cells and endothelial cells express high levels of PTX3 in COVID-19 patients. Increased plasma concentrations of PTX3 were detected in 96 COVID-19 patients. PTX3 emerged as a strong independent predictor of 28-day mortality in multivariable analysis, better than conventional markers of inflammation, in hospitalized COVID-19 patients. The prognostic significance of PTX3 abundance for mortality was confirmed in a second independent cohort (54 patients). Thus, circulating and lung myelomonocytic cells and endothelial cells are a major source of PTX3, and PTX3 plasma concentration can serve as an independent strong prognostic indicator of short-term mortality in COVID-19.

2020-10-29 | GSE160351 | GEO

Control of Complement Activation by the Long Pentraxin PTX3: Implications in Age-Related Macular Degeneration.

Project description:Dysregulation of the complement system is central to age-related macular degeneration (AMD), the leading cause of blindness in the developed world. Most of the genetic variation associated with AMD resides in complement genes, with the greatest risk associated with polymorphisms in the complement factor H (CFH) gene; factor H (FH) is the major inhibitor of the alternative pathway (AP) of complement that specifically targets C3b and the AP C3 convertase. Long pentraxin 3 (PTX3) is a soluble pattern recognition molecule that has been proposed to inhibit AP activation via recruitment of FH. Although present in the human retina, if and how PTX3 plays a role in AMD is still unclear. In this work we demonstrated the presence of PTX3 in the human vitreous and studied the PTX3-FH-C3b crosstalk and its effects on complement activation in a model of retinal pigment epithelium (RPE). RPE cells cultured in inflammatory AMD-like conditions overexpressed the PTX3 protein, and up-regulated AP activating genes. PTX3 bound RPE cells in a physiological setting, however this interaction was reduced in inflammatory conditions, whereby PTX3 had no complement-inhibiting activity on inflamed RPE. However, on non-cellular surfaces, PTX3 formed a stable ternary complex with FH and C3b that acted as a "hot spot" for complement inhibition. Our findings suggest a protective role for PTX3 in response to complement dysregulation in AMD and point to a novel mechanism of complement regulation by this pentraxin with potential implications in pathology and pharmacology of AMD.

| S-EPMC7725797 | biostudies-literature

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