title: Pulmonary injury after combined exposures to low-dose low-LET radiation and fungal spores.
abstract: Exposure to infectious microbes is a likely confounder after a nuclear terrorism event. In combination with radiation, morbidity and mortality from an infection may increase significantly. Pulmonary damage after low-dose low-LET irradiation is characterized by an initial diffuse alveolar inflammation. By contrast, inhaled fungal spores produce localized damage around pulmonary bronchioles. In the present study, we assessed lung injury in C57BL/6 mice after combined exposures to whole-body X radiation and inhaled fungal spores. Either animals were exposed to Aspergillus spores and immediately irradiated with 2 Gy, or the inoculation and irradiation were separated by 8 weeks. Pulmonary injury was assessed at 24 and 48 h and 1, 2, 4, 8, and 24 weeks later using standard H&E-stained sections and compared with sham-treated age-matched controls. Immunohistochemistry for invasive inflammatory cells (macrophages, neutrophils and B and T lymphocytes) was performed. A semi-quantitative assessment of pulmonary injury was made using three distinct parameters: local infiltration of inflammatory cells, diffuse inflammation, and thickening and distortion of alveolar architecture. Radiation-induced changes in lung architecture were most evident during the first 2 weeks postexposure. Fungal changes were seen over the first 4 weeks. Simultaneous combined exposures significantly increased the duration of acute pulmonary damage up to 24 weeks (P < 0.01). In contrast, administration of the fungus 8 weeks after irradiation did not produce enhanced levels of acute pulmonary damage. These data imply that the inhalation of fungal spores at the time of a radiation exposure alters the susceptibility of the lungs to radiation-induced injury.
authors.affiliation: Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan 48073, USA. brian.marples@beaumont.edu
authors.forename: B
authors.initials: B
authors.lastname: Marples
authors.forename: L
authors.initials: L
authors.lastname: Downing
authors.forename: K E
authors.initials: KE
authors.lastname: Sawarynski
authors.forename: J N
authors.initials: JN
authors.lastname: Finkelstein
authors.forename: J P
authors.initials: JP
authors.lastname: Williams
authors.forename: A A
authors.initials: AA
authors.lastname: Martinez
authors.forename: G D
authors.initials: GD
authors.lastname: Wilson
authors.forename: M D
authors.initials: MD
authors.lastname: Sims
mesh_terms: D000818:Animals; D001232:Aspergillus fumigatus / Q000502:physiology*; D004781:Environmental Exposure / Q000009:adverse effects; D005260:Female; D018499:Linear Energy Transfer; D055370:Lung Injury / Q000209:etiology* / Q000382:microbiology* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011829:Radiation Dosage; D013172:Spores, Fungal / Q000502:physiology; D014916:Whole-Body Irradiation / Q000009:adverse effects*