The Experts below are selected from a list of 7128 Experts worldwide ranked by ideXlab platform
Alberto Mantovani - One of the best experts on this subject based on the ideXlab platform.
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the long Pentraxin ptx3 as a humoral innate immunity functional player and biomarker of infections and sepsis
Frontiers in Immunology, 2019Co-Authors: Remi Porte, Alberto Mantovani, Cecilia Garlanda, Sadaf Davoudian, Fatemeh Asgari, Raffaella Parente, Barbara BottazziAbstract: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.
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the long Pentraxin ptx3 as a link between innate immunity tissue remodeling and cancer
Frontiers in Immunology, 2019Co-Authors: Andrea Doni, Alberto Mantovani, Cecilia Garlanda, Antonio Inforzato, Elena Magrini, Matteo Stravalaci, Barbara BottazziAbstract: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 defence 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 remodelling support the view that microbial and matrix recognition are evolutionarily conserved functions of humoral innate immunity molecules.
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the Pentraxins ptx3 and sap in innate immunity regulation of inflammation and tissue remodelling
Journal of Hepatology, 2016Co-Authors: Barbara Bottazzi, Cecilia Garlanda, Antonio Inforzato, Massimo Messa, Marialuisa Barbagallo, Elena Magrini, Alberto MantovaniAbstract:Summary Pentraxins are a superfamily of fluid phase pattern recognition molecules conserved in evolution and characterized by a cyclic multimeric structure. C-reactive protein (CRP) and serum amyloid P component (SAP) constitute the short Pentraxin arm of the superfamily. CRP and SAP are produced in the liver in response to IL-6 and are acute phase reactants in humans and mice respectively. In addition SAP has been shown to affect tissue remodelling and fibrosis by stabilizing all types of amyloid fibrils and by regulating monocyte to fibrocyte differentiation. Pentraxin 3 (PTX3) is the prototype of the long Pentraxin arm. Gene targeted mice and genetic and epigenetic studies in humans suggest that PTX3 plays essential non-redundant roles in innate immunity and inflammation as well as in tissue remodelling. Recent studies have revealed the role of PTX3 as extrinsic oncosuppressor, able to tune cancer-related inflammation. In addition, at acidic pH PTX3 can interact with provisional matrix components promoting inflammatory matrix remodelling. Thus acidification during tissue repair sets PTX3 in a tissue remodelling and repair mode, suggesting that matrix and microbial recognition are common, ancestral features of the humoral arm of innate immunity.
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The yin-yang of long Pentraxin PTX3 in inflammation and immunity.
Immunology Letters, 2014Co-Authors: Kenji Daigo, Alberto Mantovani, Barbara BottazziAbstract:Pentraxins are a family of multimeric proteins characterized by the presence of a Pentraxin signature in their C-terminus region. Based on the primary structure, Pentraxins are divided into short and long Pentraxin: C-reactive protein (CRP) is the prototype of the short Pentraxin subfamily while Pentraxin 3 (PTX3) is the prototypic long Pentraxin. Despite these two molecules exert similar fundamental actions in the regulation of innate immune and inflammatory responses, several differences exist between CRP and PTX3, including gene organization, protein oligomerization and expression pattern. The pathophysiological roles of PTX3 have been investigated using genetically modified mice since PTX3 gene organization and regulation are well conserved between mouse and human. Such in vivo studies figured out that PTX3 mainly have host-protective effects, even if it could also exert negative effects under certain pathophysiologic conditions. Here we will review the general properties of CRP and PTX3, emphasizing the differences between the two molecules and the regulatory functions exerted by PTX3 in innate immunity and inflammation.
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the long Pentraxin ptx3 as a key component of humoral innate immunity and a candidate diagnostic for inflammatory diseases
International Archives of Allergy and Immunology, 2014Co-Authors: Sébastien Jaillon, Cecilia Garlanda, Stefania Gentile, Eduardo Bonavita, Marcello Rubino, Ilaria Laface, Alberto MantovaniAbstract:The innate immune system is composed of a cellular arm and a humoral arm. Components of the humoral arm include members of the complement cascade and soluble pattern recognition molecules (PRMs). These PRMs recognize pathogen-associated molecular patterns and are functional ancestors of antibodies, playing a role in complement activation, opsonization and agglutination. Pentraxins consist of a set of multimeric soluble proteins and represent the prototypic components of humoral innate immunity. The prototypic long Pentraxin PTX3 is highly conserved in evolution and produced by somatic and innate immune cells after proinflammatory stimuli. PTX3 interacts with a set of self, nonself and modified self ligands and exerts essential roles in innate immunity, inflammation control and matrix deposition. In addition, translational studies suggest that PTX3 may be a useful biomarker of human pathologies complementary to C-reactive protein. In this study, we will review the general functions of Pentraxins in innate immunity and inflammation, focusing our attention on the prototypic long Pentraxin PTX3.
Barbara Bottazzi - One of the best experts on this subject based on the ideXlab platform.
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the long Pentraxin ptx3 as a humoral innate immunity functional player and biomarker of infections and sepsis
Frontiers in Immunology, 2019Co-Authors: Remi Porte, Alberto Mantovani, Cecilia Garlanda, Sadaf Davoudian, Fatemeh Asgari, Raffaella Parente, Barbara BottazziAbstract: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.
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the long Pentraxin ptx3 as a link between innate immunity tissue remodeling and cancer
Frontiers in Immunology, 2019Co-Authors: Andrea Doni, Alberto Mantovani, Cecilia Garlanda, Antonio Inforzato, Elena Magrini, Matteo Stravalaci, Barbara BottazziAbstract: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 defence 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 remodelling support the view that microbial and matrix recognition are evolutionarily conserved functions of humoral innate immunity molecules.
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the Pentraxins ptx3 and sap in innate immunity regulation of inflammation and tissue remodelling
Journal of Hepatology, 2016Co-Authors: Barbara Bottazzi, Cecilia Garlanda, Antonio Inforzato, Massimo Messa, Marialuisa Barbagallo, Elena Magrini, Alberto MantovaniAbstract:Summary Pentraxins are a superfamily of fluid phase pattern recognition molecules conserved in evolution and characterized by a cyclic multimeric structure. C-reactive protein (CRP) and serum amyloid P component (SAP) constitute the short Pentraxin arm of the superfamily. CRP and SAP are produced in the liver in response to IL-6 and are acute phase reactants in humans and mice respectively. In addition SAP has been shown to affect tissue remodelling and fibrosis by stabilizing all types of amyloid fibrils and by regulating monocyte to fibrocyte differentiation. Pentraxin 3 (PTX3) is the prototype of the long Pentraxin arm. Gene targeted mice and genetic and epigenetic studies in humans suggest that PTX3 plays essential non-redundant roles in innate immunity and inflammation as well as in tissue remodelling. Recent studies have revealed the role of PTX3 as extrinsic oncosuppressor, able to tune cancer-related inflammation. In addition, at acidic pH PTX3 can interact with provisional matrix components promoting inflammatory matrix remodelling. Thus acidification during tissue repair sets PTX3 in a tissue remodelling and repair mode, suggesting that matrix and microbial recognition are common, ancestral features of the humoral arm of innate immunity.
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The yin-yang of long Pentraxin PTX3 in inflammation and immunity.
Immunology Letters, 2014Co-Authors: Kenji Daigo, Alberto Mantovani, Barbara BottazziAbstract:Pentraxins are a family of multimeric proteins characterized by the presence of a Pentraxin signature in their C-terminus region. Based on the primary structure, Pentraxins are divided into short and long Pentraxin: C-reactive protein (CRP) is the prototype of the short Pentraxin subfamily while Pentraxin 3 (PTX3) is the prototypic long Pentraxin. Despite these two molecules exert similar fundamental actions in the regulation of innate immune and inflammatory responses, several differences exist between CRP and PTX3, including gene organization, protein oligomerization and expression pattern. The pathophysiological roles of PTX3 have been investigated using genetically modified mice since PTX3 gene organization and regulation are well conserved between mouse and human. Such in vivo studies figured out that PTX3 mainly have host-protective effects, even if it could also exert negative effects under certain pathophysiologic conditions. Here we will review the general properties of CRP and PTX3, emphasizing the differences between the two molecules and the regulatory functions exerted by PTX3 in innate immunity and inflammation.
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The long Pentraxin PTX3: a paradigm for humoral pattern recognition molecules
Annals of the New York Academy of Sciences, 2013Co-Authors: Alberto Mantovani, Barbara Bottazzi, Sonia Valentino, Antonio Inforzato, Stefania Gentile, Cecilia GarlandaAbstract:Pattern recognition molecules (PRMs) are components of the humoral arm of innate immunity; they recognize pathogen-associated molecular patterns (PAMP) and are functional ancestors of antibodies, promoting complement activation, opsonization, and agglutination. In addition, several PRMs have a regulatory function on inflammation. Pentraxins are a family of evolutionarily conserved PRMs characterized by a cyclic multimeric structure. On the basis of structure, Pentraxins have been operationally divided into short and long families. C-reactive protein (CRP) and serum amyloid P component are prototypes of the short Pentraxin family, while Pentraxin 3 (PTX3) is a prototype of the long Pentraxins. PTX3 is produced by somatic and immune cells in response to proinflammatory stimuli and Toll-like receptor engagement, and it interacts with several ligands and exerts multifunctional properties. Unlike CRP, PTX3 gene organization and regulation have been conserved in evolution, thus allowing its pathophysiological roles to be evaluated in genetically modified animals. Here we will briefly review the general properties of CRP and PTX3 as prototypes of short and long Pentraxins, respectively, emphasizing in particular the functional role of PTX3 as a prototypic PRM with antibody-like properties.
Cecilia Garlanda - One of the best experts on this subject based on the ideXlab platform.
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the long Pentraxin ptx3 as a humoral innate immunity functional player and biomarker of infections and sepsis
Frontiers in Immunology, 2019Co-Authors: Remi Porte, Alberto Mantovani, Cecilia Garlanda, Sadaf Davoudian, Fatemeh Asgari, Raffaella Parente, Barbara BottazziAbstract: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.
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the long Pentraxin ptx3 as a link between innate immunity tissue remodeling and cancer
Frontiers in Immunology, 2019Co-Authors: Andrea Doni, Alberto Mantovani, Cecilia Garlanda, Antonio Inforzato, Elena Magrini, Matteo Stravalaci, Barbara BottazziAbstract: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 defence 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 remodelling support the view that microbial and matrix recognition are evolutionarily conserved functions of humoral innate immunity molecules.
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the Pentraxins ptx3 and sap in innate immunity regulation of inflammation and tissue remodelling
Journal of Hepatology, 2016Co-Authors: Barbara Bottazzi, Cecilia Garlanda, Antonio Inforzato, Massimo Messa, Marialuisa Barbagallo, Elena Magrini, Alberto MantovaniAbstract:Summary Pentraxins are a superfamily of fluid phase pattern recognition molecules conserved in evolution and characterized by a cyclic multimeric structure. C-reactive protein (CRP) and serum amyloid P component (SAP) constitute the short Pentraxin arm of the superfamily. CRP and SAP are produced in the liver in response to IL-6 and are acute phase reactants in humans and mice respectively. In addition SAP has been shown to affect tissue remodelling and fibrosis by stabilizing all types of amyloid fibrils and by regulating monocyte to fibrocyte differentiation. Pentraxin 3 (PTX3) is the prototype of the long Pentraxin arm. Gene targeted mice and genetic and epigenetic studies in humans suggest that PTX3 plays essential non-redundant roles in innate immunity and inflammation as well as in tissue remodelling. Recent studies have revealed the role of PTX3 as extrinsic oncosuppressor, able to tune cancer-related inflammation. In addition, at acidic pH PTX3 can interact with provisional matrix components promoting inflammatory matrix remodelling. Thus acidification during tissue repair sets PTX3 in a tissue remodelling and repair mode, suggesting that matrix and microbial recognition are common, ancestral features of the humoral arm of innate immunity.
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the long Pentraxin ptx3 as a key component of humoral innate immunity and a candidate diagnostic for inflammatory diseases
International Archives of Allergy and Immunology, 2014Co-Authors: Sébastien Jaillon, Cecilia Garlanda, Stefania Gentile, Eduardo Bonavita, Marcello Rubino, Ilaria Laface, Alberto MantovaniAbstract:The innate immune system is composed of a cellular arm and a humoral arm. Components of the humoral arm include members of the complement cascade and soluble pattern recognition molecules (PRMs). These PRMs recognize pathogen-associated molecular patterns and are functional ancestors of antibodies, playing a role in complement activation, opsonization and agglutination. Pentraxins consist of a set of multimeric soluble proteins and represent the prototypic components of humoral innate immunity. The prototypic long Pentraxin PTX3 is highly conserved in evolution and produced by somatic and innate immune cells after proinflammatory stimuli. PTX3 interacts with a set of self, nonself and modified self ligands and exerts essential roles in innate immunity, inflammation control and matrix deposition. In addition, translational studies suggest that PTX3 may be a useful biomarker of human pathologies complementary to C-reactive protein. In this study, we will review the general functions of Pentraxins in innate immunity and inflammation, focusing our attention on the prototypic long Pentraxin PTX3.
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The long Pentraxin PTX3: a paradigm for humoral pattern recognition molecules
Annals of the New York Academy of Sciences, 2013Co-Authors: Alberto Mantovani, Barbara Bottazzi, Sonia Valentino, Antonio Inforzato, Stefania Gentile, Cecilia GarlandaAbstract:Pattern recognition molecules (PRMs) are components of the humoral arm of innate immunity; they recognize pathogen-associated molecular patterns (PAMP) and are functional ancestors of antibodies, promoting complement activation, opsonization, and agglutination. In addition, several PRMs have a regulatory function on inflammation. Pentraxins are a family of evolutionarily conserved PRMs characterized by a cyclic multimeric structure. On the basis of structure, Pentraxins have been operationally divided into short and long families. C-reactive protein (CRP) and serum amyloid P component are prototypes of the short Pentraxin family, while Pentraxin 3 (PTX3) is a prototype of the long Pentraxins. PTX3 is produced by somatic and immune cells in response to proinflammatory stimuli and Toll-like receptor engagement, and it interacts with several ligands and exerts multifunctional properties. Unlike CRP, PTX3 gene organization and regulation have been conserved in evolution, thus allowing its pathophysiological roles to be evaluated in genetically modified animals. Here we will briefly review the general properties of CRP and PTX3 as prototypes of short and long Pentraxins, respectively, emphasizing in particular the functional role of PTX3 as a prototypic PRM with antibody-like properties.
Andrea Doni - One of the best experts on this subject based on the ideXlab platform.
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the long Pentraxin ptx3 as a link between innate immunity tissue remodeling and cancer
Frontiers in Immunology, 2019Co-Authors: Andrea Doni, Alberto Mantovani, Cecilia Garlanda, Antonio Inforzato, Elena Magrini, Matteo Stravalaci, Barbara BottazziAbstract: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 defence 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 remodelling support the view that microbial and matrix recognition are evolutionarily conserved functions of humoral innate immunity molecules.
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ptx3 as a paradigm for the interaction of Pentraxins with the complement system
Seminars in Immunology, 2013Co-Authors: Antonio Inforzato, Cecilia Garlanda, Barbara Bottazzi, Andrea Doni, Isabella Barajon, Roberto Leone, Alberto MantovaniAbstract:Abstract Pentraxins are highly conserved components of the humoral arm of innate immunity. They include the short Pentraxins C reactive protein (CRP) and serum amyloid P component (SAP), and the long Pentraxin PTX3. These are soluble pattern-recognition molecules that are present in the blood and body fluids, and share the ability to recognize pathogens and promote their disposal. CRP and SAP are produced systemically in the liver while PTX3 is produced locally in a number of tissues, macrophages and neutrophils being major sources of this long Pentraxin. Pentraxins interact with components of the classical and lectin pathways of Complement as well as with Complement regulators. In particular, PTX3 recognizes C1q, factor H, MBL and ficolins, where these interactions amplify the repertoire of microbial recognition and effector functions of the Complement system. The complex interaction of Pentraxins with the Complement system at different levels has broad implications for host defence and regulation of inflammation.
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M-ficolin interacts with the long Pentraxin PTX3: a novel case of cross-talk between soluble pattern-recognition molecules.
Journal of Immunology, 2011Co-Authors: Evelyne Gout, Alberto Mantovani, Andrea Doni, Christine Moriscot, Chantal Dumestre-pérard, Monique Lacroix, Julien Pérard, Guy Schoehn, Gérard J Arlaud, Nicole ThielensAbstract:Ficolins and Pentraxins are soluble oligomeric pattern-recognition molecules that sense danger signals from pathogens and altered self-cells and might act synergistically in innate immune defense and maintenance of immune tolerance. The interaction of M-ficolin with the long Pentraxin Pentraxin 3 (PTX3) has been characterized using surface plasmon resonance spectroscopy and electron microscopy. M-ficolin was shown to bind PTX3 with high affinity in the presence of calcium ions. The interaction was abolished in the presence of EDTA and inhibited by N-acetyl-D-glucosamine, indicating involvement of the fibrinogen-like domain of M-ficolin. Removal of sialic acid from the single N-linked carbohydrate of the C-terminal domain of PTX3 abolished the interaction. Likewise, an M-ficolin mutant with impaired sialic acid-binding ability did not interact with PTX3. Interaction was also impaired when using the isolated recognition domain of M-ficolin or the monomeric C-terminal domain of PTX3, indicating requirement for oligomerization of both proteins. Electron microscopy analysis of the M-ficolin-PTX3 complexes revealed that the M-ficolin tetramer bound up to four PTX3 molecules. From a functional point of view, immobilized PTX3 was able to trigger M-ficolin-dependent activation of the lectin complement pathway. These data indicate that interaction of M-ficolin with PTX3 arises from its ability to bind sialylated ligands and thus differs from the binding to the short Pentraxin C-reactive protein and from the binding of L-ficolin to PTX3. The M-ficolin-PTX3 interaction described in this study represents a novel case of cross-talk between soluble pattern-recognition molecules, lending further credit to the integrated view of humoral innate immunity that emerged recently.
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heterocomplexes of mannose binding lectin and the Pentraxins ptx3 or serum amyloid p component trigger cross activation of the complement system
Journal of Biological Chemistry, 2011Co-Authors: Andrea Doni, Alberto Mantovani, Mikkelole Skjoedt, Christian Honore, M C Arendrup, Peter GarredAbstract:The long Pentraxin 3 (PTX3), serum amyloid P component (SAP), and C-reactive protein belong to the Pentraxin family of pattern recognition molecules involved in tissue homeostasis and innate immunity. They interact with C1q from the classical complement pathway. Whether this also occurs via the analogous mannose-binding lectin (MBL) from the lectin complement pathway is unknown. Thus, we investigated the possible interaction between MBL and the Pentraxins. We report that MBL bound PTX3 and SAP partly via its collagen-like domain but not C-reactive protein. MBL-PTX3 complex formation resulted in recruitment of C1q, but this was not seen for the MBL-SAP complex. However, both MBL-PTX3 and MBL-SAP complexes enhanced C4 and C3 deposition and opsonophagocytosis of Candida albicans by polymorphonuclear leukocytes. Interaction between MBL and PTX3 led to communication between the lectin and classical complement pathways via recruitment of C1q, whereas SAP-enhanced complement activation occurs via a hitherto unknown mechanism. Taken together, MBL-Pentraxin heterocomplexes trigger cross-activation of the complement system.
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role of complement and fcγ receptors in the protective activity of the long Pentraxin ptx3 against aspergillus fumigatus
Blood, 2010Co-Authors: Federica Moalli, Alberto Mantovani, Barbara Bottazzi, Livija Deban, Andrea Doni, Teresa Zelante, S Zagarella, Luigina Romani, Cecilia GarlandaAbstract:Pentraxin 3 (PTX3) is a soluble pattern recognition molecule playing a nonredundant role in resistance against Aspergillus fumigatus. The present study was designed to investigate the molecular pathways involved in the opsonic activity of PTX3. The PTX3 N-terminal domain was responsible for conidia recognition, but the full-length molecule was necessary for opsonic activity. The PTX3-dependent pathway of enhanced neutrophil phagocytic activity involved complement activation via the alternative pathway; Fcγ receptor (FcγR) IIA/CD32 recognition of PTX3-sensitized conidia and complement receptor 3 (CR3) activation; and CR3 and CD32 localization to the phagocytic cup. Gene targeted mice (ptx3, FcR common γ chain, C3, C1q) validated the in vivo relevance of the pathway. In particular, the protective activity of exogenous PTX3 against A fumigatus was abolished in FcR common γ chain-deficient mice. Thus, the opsonic and antifungal activity of PTX3 is at the crossroad between complement, complement receptor 3-, and FcγR-mediated recognition. Because short Pentraxins (eg, C-reactive protein) interact with complement and FcγR, the present results may have general significance for the mode of action of these components of the humoral arm of innate immunity.
Giuseppe Peri - One of the best experts on this subject based on the ideXlab platform.
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Pentraxin 3 in acute respiratory distress syndrome an early marker of severity
Critical Care Medicine, 2008Co-Authors: Tommaso Mauri, Giuseppe Peri, Alberto Mantovani, Andrea Coppadoro, Giacomo Bellani, M Bombino, Nicolò Patroniti, Antonio PesentiAbstract:Objective: Pentraxin 3 is a fluid phase receptor involved in innate immunity. It belongs to the Pentraxins family, as C-reactive protein does. Pentraxin 3 is produced by a variety of tissue cells, whereas only the liver produces C-reactive protein. Pentraxin 3 plays a unique role in the regulation of inflammation. Acute lung injury and acute respiratory distress syndrome are characterized by an important inflammatory reaction. We investigated the role of Pentraxin 3 as a marker of severity and outcome predictor of acute lung injury and acute respiratory distress syndrome. Design: We measured circulating Pentraxin 3 and C-reactive protein levels within 24 hrs from intubation (day 1), after 24 hrs from the first sample, then every 3 days for the first month and then once a week, until discharge from the intensive care unit. Pentraxin 3 was also measured in bronchoalveolar lavages, performed when clinically indicated. Setting: One university medical center general intensive care unit. Patients: The study included 21 patients affected by acute lung injury and acute respiratory distress syndrome (1994 Consensus Conference criteria). Interventions: None. Measurements and Main Results: Pentraxin 3 plasma levels were high with a peak on the first day (median 71.05 ng/mL, interquartile range 52.37-117.38 ng/mL, normal values <2 ng/mL), declining thereafter. C-reactive protein peaked later and remained at relatively high values. Out of several day 1 parameters, Pentraxin 3 was the only significant difference between survivors and nonsurvivors. Pentraxin 3 levels were positively correlated with lung injury score values (p < 0.001) and number of organ failures (p < 0.001). Pentraxin 3 was present in bronchoalveolar lavages fluids (5.03 ng/mL, interquartile range 1.52-8.48 ng/mL) and bronchoalveolar lavages positive to bacterial culture were associated with significantly higher Pentraxin 3 values (p < 0.05). Conclusions: The results presented here show that Pentraxin 3 is elevated in acute lung injury and acute respiratory distress syndrome and that its levels correlate with parameters of lung injury and systemic involvement. The clinical and pathophysio-logical significance of Pentraxin 3 in acute lung injury and acute respiratory distress syndrome deserves further scrutiny.
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Pentraxin 3 in acute respiratory distress syndrome: an early marker of severity.
Critical Care Medicine, 2008Co-Authors: Tommaso Mauri, Giuseppe Peri, Alberto Mantovani, Andrea Coppadoro, Giacomo Bellani, M Bombino, Nicolò Patroniti, Antonio PesentiAbstract:Objective: Pentraxin 3 is a fluid phase receptor involved in innate immunity. It belongs to the Pentraxins family, as C-reactive protein does. Pentraxin 3 is produced by a variety of tissue cells, whereas only the liver produces C-reactive protein. Pentraxin 3 plays a unique role in the regulation of inflammation. Acute lung injury and acute respiratory distress syndrome are characterized by an important inflammatory reaction. We investigated the role of Pentraxin 3 as a marker of severity and outcome predictor of acute lung injury and acute respiratory distress syndrome. Design: We measured circulating Pentraxin 3 and C-reactive protein levels within 24 hrs from intubation (day 1), after 24 hrs from the first sample, then every 3 days for the first month and then once a week, until discharge from the intensive care unit. Pentraxin 3 was also measured in bronchoalveolar lavages, performed when clinically indicated. Setting: One university medical center general intensive care unit. Patients: The study included 21 patients affected by acute lung injury and acute respiratory distress syndrome (1994 Consensus Conference criteria). Interventions: None. Measurements and Main Results: Pentraxin 3 plasma levels were high with a peak on the first day (median 71.05 ng/mL, interquartile range 52.37-117.38 ng/mL, normal values
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The long Pentraxin PTX3 in vascular pathology.
Vascular Pharmacology, 2006Co-Authors: Alberto Mantovani, Giuseppe Peri, Yeny Martinez De La Torre, Cecilia Garlanda, Barbara Bottazzi, Andrea Doni, Roberto LatiniAbstract: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.
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elevated plasma levels of the long Pentraxin Pentraxin 3 in severe dengue virus infections
Journal of Medical Virology, 2005Co-Authors: Albert T A Mairuhu, Giuseppe Peri, Tatty E Setiati, Erik C Hack, Penelopie Koraka, Augustinus Soemantri, Albert D M E Osterhaus, Dees P M Brandjes, Jos W M Van Der Meer, Alberto MantovaniAbstract: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.
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Non-redundant role of the long Pentraxin PTX3 in anti-fungal innate immune response
Nature, 2002Co-Authors: Cecilia Garlanda, Barbara Bottazzi, Emilio Hirsch, Silvia Bozza, Antonietta Salustri, Marika De Acetis, Rachele Nota, Alessia Maccagno, Federica Riva, Giuseppe PeriAbstract:Pentraxins are a superfamily of conserved proteins that are characterized by a cyclic multimeric structure1. 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 mediators2,3,4. Short Pentraxins regulate innate resistance to microbes and the scavenging of cellular debris and extracellular matrix components2,3,4,5. 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 ability6. 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.