Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Mycopathologia. 2011 Jul;172(1):5-15. doi: 10.1007/s11046-011-9400-3. Epub 2011 Apr 20.
Stachybotrys chartarum, a ubiquitous fungus in our environment, has been suspected of causing respiratory symptoms in humans, such as acute infant pulmonary hemorrhage and asthma. We previously established a mouse model in which repeated inhalation of Stachybotrys chartarum spores caused pulmonary hypertension. To further investigate the model, particularly in the pulmonary circulation, mice were intra-tracheally injected with spores, 18 times over 12 weeks. Severe muscularization was observed in the small- to medium-sized pulmonary arteries. Bronchoalveolar lavage fluid revealed an increase in eosinophils accompanied by high concentrations of Th2-associated cytokines, IL-4, IL-5, but not Th1-associated IFN-γ. The remodeling was temporary, resolving after cessation of spore inhalation. Chronic inhibition of the RhoA/Rho-kinase pathway by fasudil attenuated pulmonary arterial remodeling. These data suggest that Stachybotrys-mediated remodeling is caused by Th2-associated inflammation and can be resolved by Rho-kinase inhibition, either through direct effects on smooth muscle hypertrophy or through indirect effects on vascular inflammation. These data also show that extensive pulmonary vascular remodeling, often thought of as a fixed lesion, will spontaneously resolve in the absence of underlying molecular etiology.
杂色曲霉菌广泛存在于我们的环境中，已被怀疑会导致人类出现呼吸道症状，如急性婴儿肺出血和哮喘。我们之前建立了一个小鼠模型，其中重复吸入杂色曲霉菌孢子会导致肺动脉高压。为了进一步研究该模型，特别是在肺循环中，我们将孢子通过气管内注射到小鼠体内，共 12 周内注射 18 次。在中小肺动脉中观察到严重的肌化。支气管肺泡灌洗液显示嗜酸性粒细胞增加，同时 Th2 相关细胞因子 IL-4、IL-5 浓度升高，但 Th1 相关 IFN-γ没有升高。这种重塑是暂时的，停止孢子吸入后会自行消退。法舒地尔（fasudil）抑制 RhoA/Rho 激酶通路可减轻肺动脉重塑。这些数据表明，杂色曲霉菌介导的重塑是由 Th2 相关炎症引起的，通过 Rho 激酶抑制可以得到缓解，这种缓解可能是通过直接作用于平滑肌肥大，也可能是通过间接作用于血管炎症。这些数据还表明，通常被认为是固定病变的广泛肺血管重塑在没有潜在分子病因的情况下会自发消退。
