title: Particulate matter induces prothrombotic microparticle shedding by human mononuclear and endothelial cells.
abstract: Particulate airborne pollution is associated with increased cardiopulmonary morbidity. Microparticles are extracellular vesicles shed by cells upon activation or apoptosis involved in physiological processes such as coagulation and inflammation, including airway inflammation. We investigated the hypothesis that particulate matter causes the shedding of microparticles by human mononuclear and endothelial cells. Cells, isolated from the blood and the umbilical cords of normal donors, were cultured in the presence of particulate from a standard reference. Microparticles were assessed in the supernatant as phosphatidylserine concentration. Microparticle-associated tissue factor was assessed by an one-stage clotting assay. Nanosight technology was used to evaluate microparticle size distribution. Particulate matter induces a dose- and time- dependent, rapid (1h) increase in microparticle generation in both cells. These microparticles express functional tissue factor. Particulate matter increases intracellular calcium concentration and phospholipase C inhibition reduces microparticle generation. Nanosight analysis confirmed that upon exposure to particulate matter both cells express particles with a size range consistent with the definition of microparticles (50-1000 nm). Exposure of mononuclear and endothelial cells to particulate matter upregulates the generation of microparticles at least partially mediated by calcium mobilization. This observation might provide a further link between airborne pollution and cardiopulmonary morbidity.
authors.affiliation: Laboratory of Respiratory Cell Biology, Department of Surgical, Medical, Molecular Pathology and Critical Area and Azienda Ospedaliero-Universitaria Pisana, Università degli Studi di Pisa, Pisa, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Neri
authors.affiliation: EPIGET - Epidemiology, Epigenetics and Toxicology Lab, - Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Pergoli
authors.affiliation: Laboratory of Respiratory Cell Biology, Department of Surgical, Medical, Molecular Pathology and Critical Area and Azienda Ospedaliero-Universitaria Pisana, Università degli Studi di Pisa, Pisa, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Petrini
authors.affiliation: EPIGET - Epidemiology, Epigenetics and Toxicology Lab, - Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy.
authors.forename: Lotte
authors.initials: L
authors.lastname: Gravendonk
authors.affiliation: Laboratory of Respiratory Cell Biology, Department of Surgical, Medical, Molecular Pathology and Critical Area and Azienda Ospedaliero-Universitaria Pisana, Università degli Studi di Pisa, Pisa, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Balia
authors.affiliation: Laboratory of Respiratory Cell Biology, Department of Surgical, Medical, Molecular Pathology and Critical Area and Azienda Ospedaliero-Universitaria Pisana, Università degli Studi di Pisa, Pisa, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Scalise
authors.affiliation: Department of Pharmaceutical Sciences and Department of Medical Sciences, Università del Piemonte Orientale, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Amoruso
authors.affiliation: Laboratory of Respiratory Cell Biology, Department of Surgical, Medical, Molecular Pathology and Critical Area and Azienda Ospedaliero-Universitaria Pisana, Università degli Studi di Pisa, Pisa, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Pedrinelli
authors.affiliation: Laboratory of Respiratory Cell Biology, Department of Surgical, Medical, Molecular Pathology and Critical Area and Azienda Ospedaliero-Universitaria Pisana, Università degli Studi di Pisa, Pisa, Italy.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Paggiaro
authors.affiliation: EPIGET - Epidemiology, Epigenetics and Toxicology Lab, - Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy; Epidemiology Unit, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Bollati
authors.affiliation: Laboratory of Respiratory Cell Biology, Department of Surgical, Medical, Molecular Pathology and Critical Area and Azienda Ospedaliero-Universitaria Pisana, Università degli Studi di Pisa, Pisa, Italy. Electronic address: alessandro.celi@med.unipi.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Celi
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism; D055252:Cell-Derived Microparticles / Q000187:drug effects*; D002478:Cells, Cultured; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D052638:Particulate Matter / Q000633:toxicity*; D010718:Phosphatidylserines / Q000378:metabolism
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter; D010718:Phosphatidylserines; D002118:Calcium
keywords: Endothelial cells; Microparticles; Mononuclear cells; Particulate matter; Thrombosis; Tissue factor