title: In vitro assessment of plutonium uptake and release using the human macrophage-like THP-1 cells.
abstract: Plutonium (Pu) intake by inhalation is one of the major potential consequences following an accident in the nuclear industry or after improvised nuclear device explosion. Macrophages are essential players in retention and clearance of inhaled compounds. However, the extent to which these phagocytic cells are involved in these processes highly depends on the solubility properties of the Pu deposited in the lungs. Our objectives were to develop an in vitro model representative of the human pulmonary macrophage capacity to internalize and release Pu compounds in presence or not of the chelating drug diethylenetriaminepentaacetate (DTPA). The monocyte cell line THP-1 was used after differentiation into macrophage-like cells. We assessed the cellular uptake of various forms of Pu which differ in their solubility, as well as the release of the internalized Pu. Results obtained with differentiated THP-1 cells are in good agreement with data from rat alveolar macrophages and fit well with in vivo data. In both cell types, Pu uptake and release depend upon Pu solubility and in all cases DTPA increases Pu release. The proposed model may provide a good complement to in vivo animal experiments and could be used in a first assessment to predict the fraction of Pu that could be potentially trapped, as well as the fraction available to chelating drugs.
authors.affiliation: Laboratory of Radio Toxicology, CEA/DRF/iRCM, Bruyères le Châtel, 91297 Arpajon, France. Electronic address: anne.vandermeeren@cea.fr.
authors.forename: Anne
authors.initials: A
authors.lastname: Van der Meeren
authors.affiliation: Laboratory of Radio Toxicology, CEA/DRF/iRCM, Bruyères le Châtel, 91297 Arpajon, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Moureau
authors.affiliation: Laboratory of Radio Toxicology, CEA/DRF/iRCM, Bruyères le Châtel, 91297 Arpajon, France.
authors.forename: David
authors.initials: D
authors.lastname: Laurent
authors.affiliation: Direction Health Security Environment & Radioprotection, AREVA, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Laroche
authors.affiliation: Laboratory of Radio Toxicology, CEA/DRF/iRCM, Bruyères le Châtel, 91297 Arpajon, France.
authors.forename: Jaime F
authors.initials: JF
authors.lastname: Angulo
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008297:Male; D004369:Pentetic Acid / Q000494:pharmacology; D010587:Phagocytosis; D011005:Plutonium / Q000737:chemistry / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D012995:Solubility
chemical_list: D002614:Chelating Agents; D011005:Plutonium; D004369:Pentetic Acid
keywords: Chelating agent; Macrophage-like cells; Model development; Plutonium uptake; in vitro release