title: Spores of Aspergillus versicolor isolated from indoor air of a moisture-damaged building provoke acute inflammation in mouse lungs.
abstract: Microbial growth in moisture-damaged buildings has been associated with respiratory health effects, and the spores of the mycotoxin producing fungus Aspergillus versicolor are frequently present in the indoor air. To characterize the potential of these spores to cause harmful respiratory effects, mice were exposed via intratracheal instillation to a single dose of the spores of A. versicolor (1 x 10(5), 1 x 10(6), 5 x 10(6), 1 x 10(7), or 1 x 10(8) spores), isolated from the indoor air of a moisture-damaged building. Inflammation and toxicity in lungs were evaluated 24 h later by assessment of biochemical markers and histopathology. The time course of the effects was investigated with the dose of 5 x 10(6) spores for up to 28 days. The exposure to the spores increased transiently proinflammatory cytokine levels (tumor necrosis factor [TNF] alpha and interleukin [IL]-6) in bronchoalveolar lavage fluid (BALF). The cytokine responses were dose and time dependent. The highest cytokine concentrations were measured at 6 h after the dose, and they returned to the control level by 3 days. Moreover, the spores of A. versicolor recruited inflammatory cells into airways: Neutrophils peaked transiently at 24 h, macrophages at 3 days, and lymphocytes at 7 days after the dosing. The inflammatory cell response did not completely disappear during the subsequent 28 days, though no histopathological changes were seen at that time point. The spores did not induce expression of inducible nitric oxide synthase in lavaged cells. Only the highest spore dose (1 x 10(8)) markedly increased serum IL-6, increased vascular leakage, and caused cytotoxicity (i.e., increased levels of albumin, total protein, lactate dehydrogenase [LDH], and hemoglobin in BALF) in the airways. In summary, the spores of A. versicolor caused acute inflammation in mouse lungs. This indicates that they have potential to provoke adverse health effects in the occupants of moisture-damaged buildings.
authors.affiliation: Laboratory of Toxicology, National Public Health Institute, PO Box 95, FIN-70701 Kuopio, Finland. Juha.Jussila@ktl.fi
authors.forename: Juha
authors.initials: J
authors.lastname: Jussila
authors.forename: Hannu
authors.initials: H
authors.lastname: Komulainen
authors.forename: Veli-Matti
authors.initials: VM
authors.lastname: Kosma
authors.forename: Aino
authors.initials: A
authors.lastname: Nevalainen
authors.forename: Jukka
authors.initials: J
authors.lastname: Pelkonen
authors.forename: Maija-Riitta
authors.initials: MR
authors.lastname: Hirvonen
mesh_terms: D000208:Acute Disease; D016902:Air Pollution, Indoor / Q000009:adverse effects* / Q000032:analysis; D000418:Albumins / Q000032:analysis; D000818:Animals; D001230:Aspergillus / Q000472:pathogenicity*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure / Q000009:adverse effects*; D004797:Enzyme-Linked Immunosorbent Assay; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011014:Pneumonia / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D013172:Spores, Fungal / Q000302:isolation & purification / Q000472:pathogenicity*; D014867:Water
chemical_list: D000418:Albumins; D016207:Cytokines; D014867:Water; D007770:L-Lactate Dehydrogenase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse