Jussila Juha, Komulainen Hannu, Kosma Veli-Matti, Nevalainen Aino, Pelkonen Jukka, Hirvonen Maija-Riitta
Laboratory of Toxicology, National Public Health Institute, PO Box 95, FIN-70701 Kuopio, Finland.
Inhal Toxicol. 2002 Dec;14(12):1261-77. doi: 10.1080/08958370290084908.
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.
受潮建筑物中的微生物生长与呼吸道健康影响有关,产生霉菌毒素的杂色曲霉的孢子经常出现在室内空气中。为了确定这些孢子导致有害呼吸道影响的可能性,通过气管内滴注法让小鼠单次接触从受潮建筑物室内空气中分离出的杂色曲霉孢子(1×10⁵、1×10⁶、5×10⁶、1×10⁷或1×10⁸个孢子)。24小时后通过评估生化标志物和组织病理学来评估肺部的炎症和毒性。用5×10⁶个孢子的剂量研究长达28天的影响时间进程。接触孢子后,支气管肺泡灌洗液(BALF)中促炎细胞因子水平(肿瘤坏死因子[TNF]α和白细胞介素[IL]-6)短暂升高。细胞因子反应具有剂量和时间依赖性。在给药后6小时测量到最高的细胞因子浓度,到3天时它们恢复到对照水平。此外,杂色曲霉的孢子将炎症细胞募集到气道中:给药后24小时中性粒细胞短暂达到峰值,3天巨噬细胞达到峰值,7天淋巴细胞达到峰值。在随后的28天内炎症细胞反应并未完全消失,尽管在该时间点未观察到组织病理学变化。孢子未诱导灌洗细胞中诱导型一氧化氮合酶的表达。只有最高的孢子剂量(1×10⁸)显著增加血清IL-6、增加血管渗漏并在气道中引起细胞毒性(即BALF中白蛋白、总蛋白、乳酸脱氢酶[LDH]和血红蛋白水平升高)。总之,杂色曲霉的孢子在小鼠肺部引起急性炎症。这表明它们有可能对受潮建筑物中的居住者引发不良健康影响。