title: Different reactivity of primary fibroblasts and endothelial cells towards crystalline silica: A surface radical matter.
abstract: Quartz is a well-known occupational fibrogenic agent able to cause fibrosis and other severe pulmonary diseases such as silicosis and lung cancer. The silicotic pathology owes its severity to the structural and chemo-physical properties of the particles such as shape, size and abundance of surface radicals. In earlier studies, we reported that significant amounts of surface radicals can be generated on crystalline silica by chemical aggression with ascorbic acid (AA), a vitamin naturally abundant in the lung surfactant, and this reaction led to enhanced cytotoxicity and production of inflammatory mediators in a macrophage cell line. However in the lung, other cells acting in the development of silicosis, like fibroblasts and endothelial cells, can come to direct contact with inhaled quartz. We investigated the cytotoxic/pro-inflammatory effects of AA-treated quartz microcrystals (QA) in human primary fibroblasts and endothelial cells as compared to unmodified microcrystals (Q). Our results show that, in fibroblasts, the abundance of surface radicals on quartz microcrystals (Q vs QA) significantly enhanced cell proliferation (with or without co-culture with macrophages), reactive oxygen species (ROS) production, NF-κB nuclear translocation, smooth muscle actin, fibronectin, Bcl-2 and tissue inhibitor of metalloproteinase-1 expression and collagen production. Contrariwise, endothelial cells reacted to the presence of quartz microcrystals independently from the abundance of surface radicals showing similar levels of cytotoxicity, ROS production, cell migration, MCP-1, ICAM-I and fibronectin gene expression when challenged with Q or QA. In conclusion, our in vitro experimental model demonstrates an important and quite unexplored direct contribute of silica surface radicals to fibroblast proliferation and fibrogenic responses.
authors.affiliation: Department of Earth, Environment and Life Sciences, University of Genova, Via Pastore 3, 16132 Genova, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Pozzolini
authors.affiliation: Department of Earth, Environment and Life Sciences, University of Genova, Via Pastore 3, 16132 Genova, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Vergani
authors.affiliation: Department of Earth, Environment and Life Sciences, University of Genova, Via Pastore 3, 16132 Genova, Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Ragazzoni
authors.affiliation: Department of Earth, Environment and Life Sciences, University of Genova, Via Pastore 3, 16132 Genova, Italy.
authors.forename: Livia
authors.initials: L
authors.lastname: Delpiano
authors.affiliation: Department of Earth, Environment and Life Sciences, University of Genova, Via Pastore 3, 16132 Genova, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Grasselli
authors.affiliation: Department of Earth, Environment and Life Sciences, University of Genova, Via Pastore 3, 16132 Genova, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Voci
authors.affiliation: Department of Earth, Environment and Life Sciences, University of Genova, Via Pastore 3, 16132 Genova, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Giovine
authors.affiliation: Department of Earth, Environment and Life Sciences, University of Genova, Via Pastore 3, 16132 Genova, Italy. Electronic address: soniascarfi@unige.it.
authors.forename: Sonia
authors.initials: S
authors.lastname: Scarfì
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000096:biosynthesis; D003460:Crystallization; D042783:Endothelial Cells / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects*; D005609:Free Radicals / Q000737:chemistry*; D006801:Humans; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D011791:Quartz / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012822:Silicon Dioxide / Q000633:toxicity*; D012829:Silicosis / Q000473:pathology*; D013499:Surface Properties; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
chemical_list: D005609:Free Radicals; D016328:NF-kappa B; D009573:Nitrites; D017382:Reactive Oxygen Species; D019715:Tissue Inhibitor of Metalloproteinase-1; D011791:Quartz; D012822:Silicon Dioxide; D003094:Collagen
keywords: Ascorbic acid; Collagen; Endothelial cells; Fibroblasts; Quartz