title: Effects of exposure to fluoro-edenite fibre pollution on the respiratory system: an in vivo model.
abstract: An increased standardised rate of mortality from pleural mesothelioma among the population of Biancavilla (Sicily, Italy) has been attributed to exposure to fluoro-edenite fibres. Our aim was to establish whether and how these fibres may induce pathological effects using an in vivo model. Lung tissue collected from 60 healthy sheep selected from six flocks habitually grazing near Biancavilla and from 10 control sheep was fixed formalin and paraffin-embedded; sections were stained with haematoxylin-eosin, Masson trichrome and Gomori argentic impregnation. Histochemical studies and immunohistochemical analysis for the localisation of TRAIL, DR5 and MMP13 were also performed. The lungs of exposed sheep exhibited fibrosis and loss of alveolar architecture with honeycombing of alveolar cavities. Fluoro-edenite fibres were detected close to the alveolar epithelium and interstitia. The parenchyma showed hyaline degeneration and strong PAS-positivity in the interstitium, proteoglycan alterations, reflecting a damaged basal membrane and an involvement of the interstitial matrix. MMP-13 was overexpressed, mainly in fibroblasts and epithelial cells, while positivity for TRAIL and DR5 was detected on alveolar surfaces and in the vascular stroma. The initial pathological event seems to involve first the alveoli and subsequently the interstitium, giving rise to classic honeycombing. The triggering event at the level of type I pneumocytes would damage the cytoplasmic membrane resulting in loss of cell elements and exposure of underlying capillaries, and eventually in a series of reactions including macrophage activation, possible release of growth factors and metaplasic reconstruction of lung alveoli. Immunopositivity for TRAIL and MMP-13 receptor suggests that apoptotic processes may also be activated by fluoro-edenite.
authors.affiliation: Dipartimento di Anatomy, Diagnostic Pathology, Forensic Medicine, Hygiene and Public Health, University of Catania, Catania, Italy. martinez@unict.it
authors.forename: G
authors.initials: G
authors.lastname: Martinez
authors.forename: C
authors.initials: C
authors.lastname: Loreto
authors.forename: V
authors.initials: V
authors.lastname: Rapisarda
authors.forename: G
authors.initials: G
authors.lastname: Masumeci
authors.forename: M
authors.initials: M
authors.lastname: Valentino
authors.forename: M L
authors.initials: ML
authors.lastname: Carnazza
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000032:analysis; D017636:Asbestos, Amphibole / Q000032:analysis / Q000633:toxicity*; D017364:Collagenases / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D006651:Histocytochemistry; D007150:Immunohistochemistry; D053509:Matrix Metalloproteinase 13; D008562:Membrane Glycoproteins / Q000032:analysis; D019016:Mineral Fibers; D011650:Pulmonary Alveoli / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000473:pathology; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis; D020545:Respiratory Mucosa / Q000737:chemistry / Q000473:pathology; D012137:Respiratory System / Q000737:chemistry / Q000473:pathology*; D012756:Sheep; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D000393:Air Pollutants; D051017:Apoptosis Regulatory Proteins; D017636:Asbestos, Amphibole; D008562:Membrane Glycoproteins; D019016:Mineral Fibers; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha; C492470:fluor-edenite; D017364:Collagenases; D053509:Matrix Metalloproteinase 13