title: Activation of alveolar macrophages after plutonium oxide inhalation in rats: involvement in the early inflammatory response.
abstract: Alveolar macrophages play an important role in the distribution, clearance and inflammatory reactions after particle inhalation, which may influence long-term events such as fibrosis and tumorigenesis. The objectives of the present study were to investigate the early inflammatory events after plutonium oxide inhalation in rats and involvement of alveolar macrophages. Lung changes were studied from 3 days to 3 months after inhalation of PuO2 of different isotopic compositions (70% or 97% 239Pu) and initial lung deposits (range 2.1 to 43.4 kBq/rat). Analyses of bronchoalveolar lavages showed early increases in the numbers of granulocytes, lymphocytes and multinucleated macrophages. The activation of macrophages was evaluated ex vivo by measurement of inflammatory mediator levels in culture supernatants. TNF-alpha and chemokine MCP-1, MIP-2 and CINC-1 production was elevated from 7 days after inhalation and remained so up to 3 months. In contrast, IL-1beta, IL-6 and IL-10 production was unchanged. At 6 weeks, pulmonary macrophage numbers and activation state were increased as observed from an immunohistochemistry study of lung sections with anti-ED1. Similarly, histological analyses of lung sections also showed evidence of inflammatory responses. In conclusion, our results indicate early inflammatory changes in the lungs of PuO2-contaminated animals and the involvement of macrophages in this process. A dose-effect relationship was observed between the amount of radionuclide inhaled or retained at the time of analysis and inflammatory mediator production by alveolar macrophages 14 days after exposure. For similar initial lung deposits, the inflammatory manifestation appears higher for 97% 239Pu than for 70% 239Pu.
authors.affiliation: CEA/DSV/IRCM/SREIT, Laboratory of Radiotoxicology, CEA/DAM-Ile de France Bruyères le Chatel, Arpajon cedex, France. anne.vandermeeren@cea.fr
authors.forename: Anne
authors.initials: A
authors.lastname: Van der Meeren
authors.forename: Françoise
authors.initials: F
authors.lastname: Tourdes
authors.forename: Olivier
authors.initials: O
authors.lastname: Grémy
authors.forename: Gérard
authors.initials: G
authors.lastname: Grillon
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Abram
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Poncy
authors.forename: Nina
authors.initials: N
authors.lastname: Griffiths
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018932:Chemokine CCL2 / Q000096:biosynthesis; D054426:Chemokine CXCL2 / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000209:etiology*; D019570:Inhalation Exposure; D008262:Macrophage Activation / Q000187:drug effects*; D016676:Macrophages, Alveolar / Q000187:drug effects*; D008297:Male; D011005:Plutonium / Q000633:toxicity*; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D054426:Chemokine CXCL2; C513296:Cxcl2 protein, rat; D014409:Tumor Necrosis Factor-alpha; C026885:plutonium dioxide; D011005:Plutonium