Sonia Valentino

Publications (9)53.7 Total impact

• Article: The long pentraxin PTX3 as a correlate of cancer-related inflammation and prognosis of malignancy in gliomas.

  Marco Locatelli, Stefano Ferrero, Filippo Martinelli Boneschi, Leonardo Boiocchi, Mario Zavanone, Sergio Maria Gaini, Lorenzo Bello, Sonia Valentino, Elisa Barbati, Manuela Nebuloni, Alberto Mantovani, Cecilia Garlanda
  [show abstract] [hide abstract]
  ABSTRACT: Inflammation is a component of glioma microenvironment. PTX3 is a component of the humoral arm of innate immunity and a candidate marker of inflammation. In the present study we assessed the expression of PTX3 in gliomas by immunohistochemistry. PTX3 expression differed across low and high-grade tumors based on histopathological diagnosis and clinical severity, positively correlating with tumor grade and severity. In a multivariate logistic regression model, only the PTX3 score was significantly associated with the presence of a high-grade tumor. Thus, PTX3 may represent a new marker of cancer-related inflammation and glioma malignancy.
  Journal of neuroimmunology 05/2013; · 2.84 Impact Factor
• Article: The long pentraxin PTX3: a paradigm for humoral pattern recognition molecules.

  Alberto Mantovani, Sonia Valentino, Stefania Gentile, Antonio Inforzato, Barbara Bottazzi, Cecilia Garlanda
  [show abstract] [hide abstract]
  ABSTRACT: 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.
  Annals of the New York Academy of Sciences 03/2013; · 3.15 Impact Factor
• Article: Pentraxins in humoral innate immunity.

  Antonio Inforzato, Barbara Bottazzi, Cecilia Garlanda, Sonia Valentino, Alberto Mantovani
  [show abstract] [hide abstract]
  ABSTRACT: Innate immunity represents the first line of defence against pathogens and plays key roles in activation and orientation of the adaptive immune response. The innate immune system comprises both a cellular and a humoral arm. Components of the humoral arm include soluble pattern recognition molecules (PRMs) that recognise pathogens associated molecular patterns (PAMPs) and initiate the immune response in coordination with the cellular arm, therefore acting as functional ancestors of antibodies. The long pentraxin PTX3 is a prototypic soluble PRM that is produced at sites of infection and inflammation by both somatic and immune cells. Gene targeting of this evolutionarily conserved protein has revealed a non-redundant role in resistance to selected pathogens. Moreover, PTX3 exerts important functions at the crossroad between innate immunity, inflammation and female fertility. Here we review the studies on PTX3, with emphasis on pathogen recognition and crosstalk with other components of the innate immune system.
  Advances in experimental medicine and biology 01/2012; 946:1-20. · 1.09 Impact Factor
• Article: The therapeutic potential of the humoral pattern recognition molecule PTX3 in chronic lung infection caused by Pseudomonas aeruginosa.

  Federica Moalli, Moira Paroni, Tania Véliz Rodriguez, Federica Riva, Nadia Polentarutti, Barbara Bottazzi, Sonia Valentino, Stefano Mantero, Manuela Nebuloni, Alberto Mantovani, Alessandra Bragonzi, Cecilia Garlanda
  [show abstract] [hide abstract]
  ABSTRACT: Chronic lung infections by Pseudomonas aeruginosa strains are a major cause of morbidity and mortality in cystic fibrosis (CF) patients. Although there is no clear evidence for a primary defect in the immune system of CF patients, the host is generally unable to clear P. aeruginosa from the airways. PTX3 is a soluble pattern recognition receptor that plays nonredundant roles in the innate immune response to fungi, bacteria, and viruses. In particular, PTX3 deficiency is associated with increased susceptibility to P. aeruginosa lung infection. To address the potential therapeutic effect of PTX3 in P. aeruginosa lung infection, we established persistent and progressive infections in mice with the RP73 clinical strain RP73 isolated from a CF patient and treated them with recombinant human PTX3. The results indicated that PTX3 has a potential therapeutic effect in P. aeruginosa chronic lung infection by reducing lung colonization, proinflammatory cytokine levels (CXCL1, CXCL2, CCL2, and IL-1β), and leukocyte recruitment in the airways. In models of acute infections and in in vitro assays, the prophagocytic effect of PTX3 was maintained in C1q-deficient mice and was lost in C3- and Fc common γ-chain-deficient mice, suggesting that facilitated recognition and phagocytosis of pathogens through the interplay between complement and FcγRs are involved in the therapeutic effect mediated by PTX3. These data suggested that PTX3 is a potential therapeutic tool in chronic P. aeruginosa lung infections, such as those seen in CF patients.
  The Journal of Immunology 03/2011; 186(9):5425-34. · 5.79 Impact Factor
• Article: Regulation of leukocyte recruitment by the long pentraxin PTX3.

  Livija Deban, Remo Castro Russo, Marina Sironi, Federica Moalli, Margherita Scanziani, Vanessa Zambelli, Ivan Cuccovillo, Antonio Bastone, Marco Gobbi, Sonia Valentino, [......], Silvio Danese, Giovanni Salvatori, Marica Sassano, Virgilio Evangelista, Barbara Rossi, Elena Zenaro, Gabriela Constantin, Carlo Laudanna, Barbara Bottazzi, Alberto Mantovani
  [show abstract] [hide abstract]
  ABSTRACT: Pentraxins are a superfamily of conserved proteins involved in the acute-phase response and innate immunity. Pentraxin 3 (PTX3), a prototypical member of the long pentraxin subfamily, is a key component of the humoral arm of innate immunity that is essential for resistance to certain pathogens. A regulatory role for pentraxins in inflammation has long been recognized, but the underlying mechanisms remain unclear. Here we report that PTX3 bound P-selectin and attenuated neutrophil recruitment at sites of inflammation. PTX3 released from activated leukocytes functioned locally to dampen neutrophil recruitment and regulate inflammation. Antibodies have glycosylation-dependent regulatory effect on inflammation. Therefore, PTX3, which is an essential component of humoral innate immunity, and immunoglobulins share functional outputs, including complement activation, opsonization and, as shown here, glycosylation-dependent regulation of inflammation.
  Nature Immunology 03/2010; 11(4):328-34. · 26.01 Impact Factor
• Article: Elevated plasma and alveolar levels of soluble receptor for advanced glycation endproducts are associated with severity of lung dysfunction in ARDS patients.

  Tommaso Mauri, Serge Masson, Andrea Pradella, Giacomo Bellani, Andrea Coppadoro, Michela Bombino, Sonia Valentino, Nicoló Patroniti, Alberto Mantovani, Antonio Pesenti, Roberto Latini
  [show abstract] [hide abstract]
  ABSTRACT: Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) are severe forms of bilateral lung inflammation with poor clinical outcomes. However, the pathophysiology of ALI/ARDS remains largely obscure. Soluble receptor for advanced glycation endproducts (sRAGE) plays a key regulatory role during the acute phase of inflammation, and baseline plasma levels of sRAGE were recently found to be associated with severity of ALI/ARDS. We analyzed, in ALI/ARDS patients, plasma and alveolar levels of sRAGE over time and the association with severity of lung injury. We enrolled 21 ALI/ARDS patients admitted to our intensive care unit (ICU) and assayed plasma sRAGE on the first 2 days after diagnosis, every three days for the first month and then once a week, until ICU discharge or death. We also measured sRAGE levels in bronchoalveolar lavage fluids, obtained when clinically indicated. At each sampling time, we recorded physiological and clinical data of the patients. Plasma sRAGE levels peaked at day 1 and decreased over time. When all samples were considered, plasma and alveolar sRAGE levels were significantly higher in patients with worse oxygenation and higher need for ventilatory support (i.e., patients with more severe lung dysfunction). Moreover, the presence of lung infection yielded higher alveolar sRAGE levels. In conclusion, we show that the plasma and alveolar levels of sRAGE in ALI/ARDS patients are correlated to lung injury severity and to lung infection. Our findings may, in time, lead to the development of more effective therapies against ALI/ARDS.
  The Tohoku Journal of Experimental Medicine 01/2010; 222(2):105-12. · 1.24 Impact Factor
• Article: The long pentraxin 3 is a soluble and cell-associated component of the human semen.

  Andrea Doni, Alessio Paffoni, Manuela Nebuloni, Guido Ragni, Fabio Pasqualini, Sonia Valentino, Silvia Bonetti, Alberto Mantovani, Edgardo Somigliana, Cecilia Garlanda
  [show abstract] [hide abstract]
  ABSTRACT: The long pentraxin 3 (PTX3) is a multifunctional soluble pattern recognition receptor, involved in several processes ranging from innate resistance and inflammation to clearance of apoptotic cells and organization of hyaluronic acid-rich extracellular matrices. PTX3 is also a novel marker in several pathological conditions of infectious, inflammatory, or autoimmune origin. This study was designed to assess whether PTX3 is expressed in the male reproductive tract and whether PTX3 interacts with human spermatozoa influencing their function. Here we show for the first time by immunohistochemistry that PTX3 is expressed in the male genital tract in perivascular connective tissue, in endothelial cells, in the interstitium, and in the cytoplasm of prostatic epithelial glandular cells; PTX3 was detectable in seminal plasma in variable levels, which correlated with the percentage of normal spermatozoa. Moreover, PTX3 binds to spermatozoa, in particular with immotile cells, localizing in the neck and in the subacrosomial region. Finally, recombinant PTX3 did not interfere with sperm motility.
  International Journal of Andrology 01/2008; 32(3):255-64. · 3.59 Impact Factor
• Article: The long pentraxin PTX3 as a link among innate immunity, inflammation, and female fertility.

  Barbara Bottazzi, Antonio Bastone, Andrea Doni, Cecilia Garlanda, Sonia Valentino, Livija Deban, Virginia Maina, Alessia Cotena, Federica Moalli, Luca Vago, Antonietta Salustri, Luigina Romani, Alberto Mantovani
  [show abstract] [hide abstract]
  ABSTRACT: The long pentraxin 3 (PTX3) is member of a complex superfamily of multifunctional proteins characterized by a cyclic multimeric structure. PTX3 is highly conserved in evolution and is produced by innate-immunity cells in response to proinflammatory signals and Toll-like receptor engagement. PTX3 plays complex, nonredundant functions in vivo, acting as a predecessor of antibodies, recognizing microbes, activating complement, facilitating pathogen recognition by phagocytes, and hence, playing a nonredundant role in resistance against selected pathogens. 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 nonredundant component of the humoral arm of innate immunity and involved in matrix deposition and female fertility.
  Journal of Leukocyte Biology 06/2006; 79(5):909-12. · 4.99 Impact Factor
• Article: Regulation of PTX3, a key component of humoral innate immunity in human dendritic cells: stimulation by IL-10 and inhibition by IFN-gamma.

  Andrea Doni, Mosca Michela, Barbara Bottazzi, Giuseppe Peri, Sonia Valentino, Nadia Polentarutti, Cecilia Garlanda, Alberto Mantovani
  [show abstract] [hide abstract]
  ABSTRACT: The protopypic long pentraxin 3 (PTX3) is a unique, humoral pattern-recognition receptor, which plays a nonredundant function in innate resistance to pathogens. Dendritic cells (DC) of myelomonocytic origin, but not plasmacytoid DC, are a major source of PTX3 in response to Toll-like receptor (TLR) engagement. The present study was designed to explore the regulation of PTX3 production in DC. PTX3 production was induced by TLR ligands, CD40 ligand, and interleukin (IL)-1beta and was suppressed by dexamethasone, 1alpha, 25-dihydroxivitamin D3, and prostaglandin E2. It was unexpected that lipopolysaccharide (LPS)-stimulated PTX3 production was enhanced by IL-10 and inhibited by IL-4 and interferon-gamma (IFN-gamma). Enhancement of PTX3 production by IL-10 was also evident when Pam3 Cys-Ser-(Lys)4.3HCl, a TLR2-TLR1 agonist, polyionisicpolycytidylic acid, a TLR3 agonist, and IL-1beta were used as stimuli. The effect of IL-10 was blocked by an anti-IL-10 monoclonal antibody (mAb) or an anti-IL-10 receptor alpha mAb, which also reduced the LPS-induced production. Thus, production of PTX3 in DC is subjected to a distinct regulatory network, with inhibition by IFN-gamma and enhancement by IL-10. The amplification by IL-10 of production of a nonredundant component of fluid-phase innate immunity mirrors the IL-10 stimulatory function on B cells in adaptive immunity. As PTX3 is also an extracellular matrix component, IL-10-enhanced PTX3 production may play a role in orchestration of tissue remodeling in chronic inflammation.
  Journal of Leukocyte Biology 05/2006; 79(4):797-802. · 4.99 Impact Factor