Chung Yong Joo, Coates Najwa Haykal, Viana Michael E, Copeland Lisa, Vesper Stephen J, Selgrade MaryJane K, Ward Marsha D W
Department of Environmental Sciences and Engineering, School of Public Health, University of North Carolina, Chapel Hill, NC 27599, USA.
Toxicology. 2005 Apr 1;209(1):77-89. doi: 10.1016/j.tox.2004.12.010. Epub 2005 Jan 21.
Indoor mold has been associated with the development of allergic asthma. Penicillium chrysogenum, a common indoor mold, is known to have several allergens and can induce allergic responses in a mouse model of allergic penicilliosis. Our hypothesis is that soluble components of P. chrysogenum (PCE) can dose-dependently induce responses typical of allergic asthma in BALB/c mice. Mice were exposed to 10, 20, 50, or 70 microg of PCE by involuntary aspiration four times over a 4-week period. Serum and bronchoalveolar lavage fluid (BALF) were collected before (day 0), and at days 1 and 3 following the final exposure. PCE-exposed mice demonstrated dose-dependent increases in: BALF total cell numbers including eosinophil, serum and BALF total IgE levels, BALF IL-5 levels, and increased severity of histopathologic lesions. A single exposure to the highest dose of PCE resulted in edema and cellular damage but not immune responses. Four exposures to Metarhizium anisopliae crude antigen (10 microg, positive control) resulted in equivalent or greater allergic asthma-like responses than those demonstrated by multiple exposures to 50 or 70 microg of PCE. Multiple exposures to 70 microg of PCE showed increased allergen-triggered immediate respiratory responses as well as non-specific airway hyperresponsiveness to methacholine as assessed by barometric whole-body plethysmography. Taken together, repeated pulmonary challenge with P. chrysogenum extract induced dose-dependent allergic asthma-like responses in mice.
室内霉菌与过敏性哮喘的发生有关。产黄青霉是一种常见的室内霉菌,已知含有多种过敏原,可在过敏性青霉病小鼠模型中诱发过敏反应。我们的假设是,产黄青霉的可溶性成分(PCE)可在剂量依赖的情况下诱导BALB/c小鼠出现典型的过敏性哮喘反应。在4周内,通过非自愿吸入法让小鼠接触10、20、50或70微克的PCE,共4次。在末次接触前(第0天)以及末次接触后的第1天和第3天收集血清和支气管肺泡灌洗液(BALF)。接触PCE的小鼠在以下方面呈现剂量依赖性增加:BALF中的总细胞数(包括嗜酸性粒细胞)、血清和BALF中的总IgE水平、BALF中的IL-5水平,以及组织病理学损伤的严重程度增加。单次接触最高剂量的PCE会导致水肿和细胞损伤,但不会引发免疫反应。四次接触绿僵菌粗抗原(10微克,阳性对照)所导致的过敏性哮喘样反应与多次接触50或70微克PCE所引发的反应相当或更强。通过气压式全身体积描记法评估,多次接触70微克PCE显示过敏原引发的即时呼吸反应增加,以及对乙酰甲胆碱的非特异性气道高反应性增加。综上所述,用产黄青霉提取物反复进行肺部激发可在小鼠中诱导剂量依赖性的过敏性哮喘样反应。