Experimental influenza virus infection, silicon dioxide polymorphs, and pulmonary fibrogenesis.
Inhalation exposure to silicon dioxide is known to result in acute lung injury followed by pulmonary fibrosis. Recently it has been shown that the acute lung damage during influenza virus infection is also followed by a fibrogenic process. To investigate the interaction between silicon dioxide and influenza virus infection, mice were intratracheally instilled with either alpha-quartz or cristobalite and 3 d later infected by aerosol inhalation with influenza A/PR8/34 virus. At 30, 60, and 90 d after infection, groups of virus infected and noninfected mice were sacrificed and their lungs assessed for total and differential lavage cell counts, lung hydroxyproline content, and morphometric analysis. The silica polymorphs did not alter the proliferation of virus in the lungs as quantitated by infectious virus titers of lung homogenates at 1, 5, 7, 10, and 13 d after infection. In noninfected animals, cristobalite was more reactive than alpha-quartz. The virus infection, in all parameters measured at all time intervals, enhanced the overall fibrogenic response of the lungs to the mineral dusts, suggestive of an additive fibrogenic model. The data demonstrate that virus infection following silicon dioxide exposure results in an interaction that leads to an enhanced fibrogenic response.
Jakab
G J
GJ
Department of Environmental Health Sciences, Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland 21205.
Hemenway
D R
DR
D000418:Albumins / Q000032:analysis; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D005260:Female; D006909:Hydroxyproline / Q000032:analysis; D009980:Influenza A virus / Q000187:drug effects / Q000502:physiology; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects; D016676:Macrophages, Alveolar / Q000187:drug effects; D051379:Mice; D009504:Neutrophils / Q000187:drug effects; D009976:Orthomyxoviridae Infections / Q000150:complications*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000209:etiology*; D011791:Quartz / Q000633:toxicity; D012822:Silicon Dioxide / Q000633:toxicity*; D013047:Specific Pathogen-Free Organisms; D014779:Virus Replication / Q000187:drug effects
D000418:Albumins; D011791:Quartz; D012822:Silicon Dioxide; D006909:Hydroxyproline