Pathogenic potential of asbestos fibres (Dr. Borelli)

Research Strand:

Immunology and molecular pathology (Biomedicine)

Violetta Borelli

Researcher in General Pathology (MED/04)

Tel: +390405584033
Fax: +390405584023
Email: borelliv@units.it

Biosketch

Violetta Borelli is Researcher in General Pathology at the University of Trieste since 2005. Violetta Borelli has a degree in Biology and a PhD Experimental Pathology from the University of Trieste. She had her research training at the University of Trieste. Among her research experiences, she has been a visiting scientist at the Department of Microbiology (prof. John Belisle) of the Colorado State University.

Her research interests focus on the mechanisms of physiopathology of inflammatory cells. Dr. Violetta Borelli studies the biological mechanism of the secretory process in phagocytes and mast cells, and the role of a selected type of secreted components, i.e. the peroxidases, in killing ingested microrganisms. In particular, her work has contributed to elucidate the role of human peroxidases in host defence against Mycobacterium tuberculosis.

During the last 10 years, Dr. Violetta Borelli reserch interests have been also focused on the study of the interaction between asbestos fibres and inflammatory cells, contributing to elucidate the composition of asbestos bodies coating and their controversial pathogenic potential. These studies have led to several publications in international peer-reviewed scientific journals,

In total, Violetta Borelli has published more than 30 papers published in international scientific journals and she also regularly provides her contribution to the scientific community as a peer-reviewer.

Info

Research

The research programs coordinated by Dr. Violetta Borelli are focused on the study of the role of inflammation/inflammatory cells in the pathogenetic activity of asbestos fibres and in other human diseases. These activities are organized in 3 main lines of research:

1) Identify an association between certain genetic polymorphisms (inflammasome related) and individual ability to form asbestos bodies after asbestos exposure.

2) Study of the mechanisms of interaction of asbestos fibres with cellular compartments of inflammatory cells (mast cells).

3) Mast cells in human health and disease: the role of mast cells and their mediators in endometriosis and in periodontal disease.

Current Projects

1) Inflammation and lung iron homeostasis and pleural mesothelioma

The presence of asbestos bodies in lung parenchyma is considered a histopathologic hallmark of past exposure to asbestos fibers of which there was a population of longer fibers. The mechanisms underlying asbestos body formation are complex, involving inflammatory responses and iron (Fe) metabolism. Thus the responsiveness to asbestos body formation is variable with some individuals appearing to be poor asbestos body formers. The aim of this project is to disclose the possible role of genetic variants of genes encoding inflammasome and iron metabolism proteins in the ability to form asbestos bodies in the population from North East Italy, who died after having developed malignant pleural mesothelioma, lung cancer or asbestosis. Our preliminary findings suggest that the NLRP1 inflammasome might contribute in the development of lung asbestos bodies in mesothelioma affected subjects. It is postulated that the NLRP1 missense variant may be considered as one of the possible host genetic factors contributing to individual variability in coating efficiency, which needs to be taken when assessing occupational exposure to asbestos.

2) Study of the mechanisms of interaction of mineral fibers with cellular compartments.

Exposure to mineral fibers is of great relevance for human health. A key event in this process is the interaction with inflammatory cells and the following generation of pro-inflammatory factors. Mast cells (MC) have been shown to interact with titanium oxide (TiO₂)and asbestos fibers. In this project we analyze the response of rat peritoneal MC challenged with the asbestos crocidolite and nanowires of TiO₂ compared with that induced by wollastonite employed as control fiber. The amount of secreted enzymes is evaluated together with the activity of fiber associated enzymes. The ultrastructural morphology of fiber-interacting RPMC is analyzed with electron microscopy.

Scanning electron microscope (SEM) appearance of RPMC exposed to mineral fibers: a9 asbestos crocidolite, b) wollastonite and c) TiO₂. Magnification: bars b = 3 µm; bars a and c = 1µm.

3) The role of mast cells and their mediators in endometriosis and human diseases

Mast cells are primarily known for their role in defense against pathogens, particularly bacteria; neutralization of venom toxins; and for triggering allergic responses and anaphylaxis. In addition to these direct effector functions, activated mast cells rapidly recruit other innate and adaptive immune cells and can participate in "tuning" the immune response. In this two projects we focus on the roles of mast cells in human two human diseases.

- In human periodontal disease there is an increase in the number of mast cells that may be participating either in the destructive events or in the defense mechanism of periodontal disease via secretion of cytokines and proteolytic enzymes. The aim of this project is to quantify the main mast cells protease, tryptase, in the peri-implant sulcus fluid of healthy and affected sites, whether it correlate degree of inflammation and clinical features of periodontium (in collaboration with the Department of Surgical, Medical and Health Sciences, University of Trieste, Trieste, Italy).

- Increasing evidence supports an involvement of mast cells either in the inflammatory process of endometriosis or in infertility, with MC mediators directly suppressing sperm motility in a potentially reversible manner. In this project we are evaluating the MCs/basophils population and their mediators in the peritoneal environment/fluid of infertile patients with endometriosis and their impact on human sperm motility. Furthermore an in vitro model of mast cells-sperm interaction in the peritoneal environment has been set up and evaluated from a functional and a morphological point of view (in collaboration with Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", 34137 Trieste, Italy).

Low-magnification SEM examination of adherence of human sperm by the human MC line LAD2

People

Paola Zacchi

RtdA researcher in General Pathology (MED/04)

Office: via Valerio 28, Edificio R-RA
Tel: 040558.8660
pzacchi@units.it

Scopus

The scientific activities of Dr. Zacchi are mostly focused on the project entitled "Evaluation of the pathogenetic potential of asbestos fibers after inertization".

The disposal of asbestos-containing wastes (ACW) represents a technical and economic challenge and a paramount environmental problem. ACWs are currently confined in controlled landfills, where the ACWs are permanently placed and buried. The amount of ACW to be disposed per year is expected to increase, but the limited number of operating national landfills, together with their limited residual storage capacity, suggests that the asbestos waste management is going to be, in the next future, a progressively growing and impelling problem. Moreover, the management of hazardous waste is extremely expensive, thus fostering bad practices of uncontrolled disposal thus endangering public health.

To effectively overcome the problems just described, it is necessary to promote the search for alternative methods to landfill disposal, also taking into account that any technique for the safe recovery of these materials can lead to decisive savings in public financial resources. Materials containing suitably inert asbestos could also represent a new resource, perfectly in line with a circular economy model. To achieve effective inertization of ACWs, three types of treatment are being studied: heat treatment, chemical treatment and mechano-chemical treatment. The proof that a specific treatment has been effective and therefore the product of inertization is devoided of any pathogenic potential cannot lag behind the rigorous examination of the structural modifications induced on the fibers (e.g. coagulation of the fibers). It is extremely important to verify the lack of any biological and genotoxic activities of the material undergoing inertization through the use of appropriate cell-free and in vivo biological systems.

In Friuli Venezia Giulia, the company “Friuliana costruzioni” has developed, in collaboration with the University of Trieste, an innovative patented methodology which allows for the inertization of asbestos fibers using a mechano-chemical approach. This process is currently carried out at the "Rinnova" pilot plant in Codroipo, already operating under an experimental regime, but which foresees expansion to an industrial-scale production plant during 2023.

The IN.P.PATO project funded by “PON Research and Innovation 2014-2020” aims to evaluate whether asbestos-containing cement wastes undergoing inertization with the Rinnova methodology have totally lost any pathogenic capacity and short-term cytotoxicity as well as also long-term pathogenic activity. Asbestos-dependent pathologies are indeed characterized by long latency periods and short-term cytotoxicity is not sufficient to exclude their pathogenicity. This demonstration can be obtained only upon carefully evaluating the biological effects associated with exposure of inert fibers on cultured cells and in "in vivo" animal models.

The project aims to evaluate the cytotoxic and genotoxic potential of the asbestos-containing wastes undergoing inertization both thermically and upon application of “Rinnova” methodology taking advantage of in vitro assays for DNA damage and in cellular models of pleura and lung.

Prof. Borelli Violetta (Research Group - Member)
borelliv@units.it

Vita Francesca (Research Group - Member)

Zacchi Paola (Research Group - Member)
pzacchi@units.it

Publications

Complete list of the publications of the Principal Investigator

Scopus

Selected papers

V. Borelli, E. Trevisan, F. Vita and G. Zabucchi. Mast Cells and Mineral Fibers: An Intimate Interaction with a Strong Pro-Inflammatory Potential. Submitted to the International Journal of Environmental Research and Public Health.
Crovella S , Moura RR, Cappellani S, Celsi F, Trevisan E, Schneider M, Brollo A, Nicastro EM, Vita F, Finotto L, Zabucchi G, Borelli V. A genetic variant of NLRP1 gene is associated with asbestos bodies burden in patients with malignant pleural mesothelioma. Accepted for publication in J Toxicol Environ Health A. Production tracking number: UTEH 1416911. DOI: 10.1080/15287394.2017.1416911.
Agostinis C, Vidergar R, Belmonte B, Mangogna A, Amadio L, Geri P, Borelli V, Zanconati F, Tedesco F, Confalonieri M, Tripodo C, Kishore U, Bulla R. Complement Protein C1q Binds to Hyaluronic Acid in the Malignant Pleural Mesothelioma Microenvironment and Promotes Tumor Growth. Front Immunol. 2017 Nov 20;8:1559.
Histopathological data of iron and calcium in the mouse lung after asbestos exposure. Trevisan E, Zabucchi G, Pascolo L, Pascotto E, Casarsa C, Lucattelli M, Lungarella G, Cavarra E, Bartalesi B, Zweyer M, Borelli V. Data Brief. 2016 Jan 21;6:769-75
Crovella S, Bianco AM, Vuch J, Zupin L, Moura RR, Trevisan E, Schneider M, Brollo A, Nicastro EM, Cosenzi A, Zabucchi G, Borelli V. Iron signature in asbestos-induced malignant pleural mesothelioma: A population-based autopsy study. J Toxicol Environ Health A. 2016;79(3):129-41.
Pascolo L, Borelli V, Canzonieri V, Gianoncelli A, Birarda G, Bedolla DE, Salomé M, Vaccari L, Calligaro C, Cotte M, Hesse B, Luisi F, Zabucchi G, Melato M, Rizzardi C. Differential protein folding and chemical changes in lung tissues exposed to asbestos or particulates. Sci Rep. 2015 Jul 10;5:12129.
Borelli V, Moura RR, Trevisan E, Crovella S. NLRP1 and NLRP3 polymorphisms in mesothelioma patients and asbestos exposed individuals a population-based autopsy study from North East Italy. Infect Agent Cancer. 2015 Aug 1;10:26.
Pascolo L, Zabucchi G, Gianoncelli A, Kourousias G, Trevisan E, Pascotto E, Casarsa C, Ryan C, Lucattelli M, Lungarella G, Cavarra E, Bartalesi B, Zweyer M, Cammisuli F, Melato M, Borelli V. Synchrotron X-ray microscopy reveals early calcium and iron interaction with crocidolite fibers in the lung of exposed mice. Toxicol Lett. 2016 Jan 22;241:111-20.
Zabucchi G, Trevisan E, Vita F, Soranzo MR, Borelli V. NOD1 and NOD2 Interact with the Phagosome Cargo in Mast Cells: A Detailed Morphological Evidence. Inflammation. 2015;38(3):1113-25.
Andolfi L, Trevisan E, Zweyer M, Prato S, Troian B, Vita F, Borelli V, Soranzo MR, Melato M, Zabucchi G. The crocidolite fibres interaction with human mesothelial cells as investigated by combining electron microscopy, atomic force and scanning near-field optical microscopy. J Microsc. 2013 Mar;249(3):173-83.

Last update: 11-07-2024 - 23:30

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