title: Macrophages as key elements of Mixed-oxide [U-Pu(O2)] distribution and pulmonary damage after inhalation?
abstract: Abstract Purpose: To investigate the consequences of alveolar macrophage (AM) depletion on Mixed OXide fuel (MOX: U, Pu oxide) distribution and clearance, as well as lung damage following MOX inhalation.
  
  
  METHODS
  Rats were exposed to MOX by nose only inhalation. AM were depleted with intratracheal administration of liposomal clodronate at 6 weeks. Lung changes, macrophage activation, as well as local and systemic actinide distribution were studied up to 3 months post-inhalation.
  
  
  RESULTS
  Clodronate administration modified excretion/retention patterns of α activity. At 3 months post-inhalation lung retention was higher in clodronate-treated rats compared to Phosphate Buffered Saline (PBS)-treated rats, and AM-associated α activity was also increased. Retention in liver was higher in clodronate-treated rats and fecal and urinary excretions were lower. Three months after inhalation, rats exhibited lung fibrotic lesions and alveolitis, with no marked differences between the two groups. Foamy macrophages of M2 subtype [inducible Nitric Oxide Synthase (iNOS) negative but galectin-3 positive] were frequently observed, in correlation with the accumulation of MOX particles. AM from all MOX-exposed rats showed increased chemokine levels as compared to sham controls.
  
  
  CONCLUSIONS
  Despite the transient reduced AM numbers in clodronate-treated animals no major differences on lung damage were observed as compared to non-treated rats after MOX inhalation. The higher lung activity retention in rats receiving clodronate seems to be part of a general inflammatory response and needs further investigation.
authors.affiliation: Laboratoire de RadioToxicologie, CEA/DSV/iRCM, Bruyères le Châtel , Arpajon , France.
authors.forename: Anne
authors.initials: A
authors.lastname: Van der Meeren
authors.forename: Agnes
authors.initials: A
authors.lastname: Moureau
authors.forename: Nina M
authors.initials: NM
authors.lastname: Griffiths
mesh_terms: D000818:Animals; D001345:Autoradiography; D018893:Bronchoalveolar Lavage; D004002:Clodronic Acid / Q000737:chemistry / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D005355:Fibrosis; D007150:Immunohistochemistry; D019570:Inhalation Exposure; D008168:Lung / Q000528:radiation effects*; D016676:Macrophages, Alveolar / Q000528:radiation effects*; D008297:Male; D011005:Plutonium / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D016207:Cytokines; D004002:Clodronic Acid; D011005:Plutonium
keywords: Actinide inhalation; lung damage; macrophage depletion