Rosenblum Lichtenstein Jamie H, Molina Ramon M, Donaghey Thomas C, Brain Joseph D
Harvard School of Public Health, Molecular and Integrative Physiological Sciences, Department of Environmental Health, 665 Huntington Ave., Building 2 Room 219, Boston, MA 02115, USA.
Am J Respir Cell Mol Biol. 2006 Oct;35(4):415-23. doi: 10.1165/rcmb.2005-0483OC. Epub 2006 May 11.
When the fungus Stachybotrys chartarum is inhaled, its mycotoxins may cause lung injury and inflammation. The severity of human responses to S. chartarum in both occupational and home settings varies widely. To explore these differences, we intratracheally instilled C3H/HeJ, BALB/c, and C57BL/6J mice with S. chartarum spores suspended in saline. One day later, the mice were humanely killed, bronchoalveolar lavage (BAL) was performed, and biochemical and cellular indicators of lung injury and inflammation were measured. BALB/c mice showed the highest myeloperoxidase activity, albumin and hemoglobin levels, and neutrophil numbers in their BAL among the three strains. BALB/c was the only strain to show significant increases in keratinocyte-derived cytokine (KC), monocyte chemotactic protein (MCP)-1, MCP-3, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, MIP-1gamma, MIP-2, RANTES, IL-1alpha, IL-1beta, IL-3, IL-6, IL-18, leukemia inhibitory factor, macrophage colony-stimulating factor, and TNF-alpha. A model of allergen-induced airway inflammation was examined to assess whether underlying allergic inflammation might contribute to increased susceptibility to S. chartarum-induced pulmonary inflammation and injury. Surprisingly, in BALB/c mice, ovalbumin-induced airway inflammation produced a protective effect against some S. chartarum-induced pulmonary responses. This is the first report of mammalian strain differences affecting responses to S. chartarum. These responses differ from those reported for LPS and other fungi. Analogous underlying genetic differences may contribute to the wide range of sensitivity to Stachybotrys among humans.
当吸入真菌链格孢菌时，其霉菌毒素可能会导致肺损伤和炎症。在职业和家庭环境中，人类对链格孢菌的反应严重程度差异很大。为了探究这些差异，我们将悬浮于盐水中的链格孢菌孢子经气管内注入C3H/HeJ、BALB/c和C57BL/6J小鼠体内。一天后，对小鼠实施安乐死，进行支气管肺泡灌洗（BAL），并测量肺损伤和炎症的生化及细胞指标。在这三个品系中，BALB/c小鼠的支气管肺泡灌洗液中的髓过氧化物酶活性、白蛋白和血红蛋白水平以及中性粒细胞数量最高。BALB/c是唯一显示角质形成细胞衍生细胞因子（KC）、单核细胞趋化蛋白（MCP）-1、MCP-3、巨噬细胞炎性蛋白（MIP）-1α、MIP-1β、MIP-1γ、MIP-2、调节激活正常T细胞表达和分泌因子（RANTES）、白细胞介素（IL）-1α、IL-1β、IL-3、IL-6、IL-１８、白血病抑制因子、巨噬细胞集落刺激因子和肿瘤坏死因子-α显著增加的品系。我们检测了变应原诱导的气道炎症模型，以评估潜在的变应性炎症是否可能导致对链格孢菌诱导的肺部炎症和损伤的易感性增加。令人惊讶的是，在BALB/c小鼠中，卵清蛋白诱导的气道炎症对某些链格孢菌诱导的肺部反应产生了保护作用。这是关于影响对链格孢菌反应的哺乳动物品系差异的首次报道。这些反应与针对脂多糖和其他真菌所报道的反应不同。类似的潜在基因差异可能导致人类对链格孢菌的敏感性差异很大。
