Department of Otology and Laryngology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts 02114, USA.
Laryngoscope. 2011 Aug;121(8):1687-701. doi: 10.1002/lary.21856.
OBJECTIVES/HYPOTHESIS: The pathophysiology underlying human olfactory disorders is poorly understood because biopsying the olfactory epithelium (OE) can be unrepresentative and extensive immunohistochemical analysis is lacking. Autopsy tissue enriches our grasp of normal and abnormal olfactory immunohistology and guides the sampling of the OE by biopsy. Furthermore, a comparison of the molecular phenotype of olfactory epithelial cells between rodents and humans will improve our ability to correlate human histopathology with olfactory dysfunction.
An immunohistochemical analysis of human olfactory tissue using a comprehensive battery of proven antibodies.
Human olfactory mucosa obtained from 21 autopsy specimens was analyzed with immunohistochemistry. The position and extent of olfactory mucosa was assayed by staining whole mounts (WMs) with neuronal markers. Sections of the OE were analyzed with an extensive group of antibodies directed against cytoskeletal proteins and transcription factors, as were surgical specimens from an esthesioneuroblastoma.
Neuron-rich epithelium is always found inferior to the cribriform plate, even at advanced age, despite the interruptions in the neuroepithelial sheet caused by patchy respiratory metaplasia. The pattern of immunostaining with our antibody panel identifies two distinct types of basal cell progenitors in human OE similar to rodents. The panel also clarifies the complex composition of esthesioneuroblastoma.
The extent of human olfactory mucosa at autopsy can easily be delineated as a function of age and neurologic disease. The similarities in human versus rodent OE will enable us to translate knowledge from experimental animals to humans and will extend our understanding of human olfactory pathophysiology.
目的/假设:人类嗅觉障碍的病理生理学机制尚不清楚,因为嗅上皮(OE)活检可能代表性不足,且缺乏广泛的免疫组织化学分析。尸检组织丰富了我们对正常和异常嗅觉免疫组织学的理解,并指导了活检时对 OE 的采样。此外,比较啮齿动物和人类嗅上皮细胞的分子表型将提高我们将人类组织病理学与嗅觉功能障碍相关联的能力。
使用经过验证的全面抗体对人类嗅组织进行免疫组织化学分析。
使用免疫组织化学分析了 21 例尸检标本获得的人类嗅黏膜。通过用神经元标志物对全层(WM)进行染色来测定嗅黏膜的位置和范围。对 OE 的切片进行了广泛的细胞骨架蛋白和转录因子抗体分析,以及嗅神经母细胞瘤的手术标本也进行了分析。
神经元丰富的上皮组织总是在下鼻甲板下方发现,即使在高龄时也是如此,尽管由于局灶性呼吸化生导致神经上皮片中断。我们的抗体面板的免疫染色模式在人类 OE 中识别出两种不同类型的基底细胞祖细胞,类似于啮齿动物。该面板还阐明了嗅神经母细胞瘤的复杂组成。
尸检时人类嗅黏膜的范围很容易根据年龄和神经疾病来划定。人类和啮齿动物 OE 之间的相似性将使我们能够将实验动物的知识转化为人类,并扩展我们对人类嗅觉病理生理学的理解。