Nickoloff B J, Kunkel S L, Burdick M, Strieter R M
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602.
Am J Pathol. 1995 Mar;146(3):580-8.
Research into the cause and pathophysiological mechanisms underlying expression of psoriatric skin lesions has been hampered by lack of an appropriate animal model for this common and enigmatic cutaneous disease. These studies characterize normal skin, pre-psoriatic skin, and psoriatic plaque skin samples transplanted onto severe combined immunodeficiency mice. In this report we document that 1), normal, prepsoriatic, and psoriatic plaque keratome skin samples can be transplanted onto severe combined immunodeficiency mice reliably with high rates of graft survival (> 85%) and with reproducible changes consistently observed over prolonged periods of engraftment; 2), after transplantation, by clinical assessment and routine light microscopy, normal skin remained essentially normal whereas pre-psoriatic skin became thicker, and psoriatic plaque skin retained its characteristic plaque-type elevation and scale; 3), by using a panel of antibodies and immunohistochemical analysis, the overall phenotype of human cell types (including immunocytes) that persisted in the transplanted skin was remarkably similar to the immunophenotype of pretransplanted skin samples; 4), clearly recognized interface zones between human and murine skin within the epidermal and dermal compartments could be identified by routine microscopy and immunostaining, with focal areas of chimerism; and 5), elevated interleukin 8 cytokine levels were present in transplanted pre-psoriatic and psoriatic plaque skin samples. We conclude that there are many similarities between pre- and post-transplanted human samples of normal and psoriatic skin that are grafted onto severe combined immunodeficiency mice. Thus, we propose that this new animal model is appropriate for additional mechanistic-type studies designed to reveal the underlying genetic/etiological abnormality, as well as better illuminate the pathophysiological basis, for this important skin disease.
由于缺乏适用于这种常见且神秘的皮肤疾病的动物模型，对银屑病皮肤病变表达的病因和病理生理机制的研究受到了阻碍。这些研究对移植到严重联合免疫缺陷小鼠身上的正常皮肤、银屑病前期皮肤和银屑病斑块皮肤样本进行了特征描述。在本报告中，我们记录了：1）正常、银屑病前期和银屑病斑块角质层皮肤样本能够可靠地移植到严重联合免疫缺陷小鼠身上，移植存活率高（>85%），并且在长时间植入过程中始终观察到可重复的变化；2）移植后，通过临床评估和常规光学显微镜检查，正常皮肤基本保持正常，而银屑病前期皮肤变厚，银屑病斑块皮肤保留其特征性的斑块样隆起和鳞屑；3）通过使用一组抗体和免疫组织化学分析，移植皮肤中持续存在的人类细胞类型（包括免疫细胞）的总体表型与移植前皮肤样本的免疫表型非常相似；4）通过常规显微镜检查和免疫染色可以在表皮和真皮层内识别出人类和小鼠皮肤之间清晰可辨的界面区域，存在嵌合的局部区域；5）移植的银屑病前期和银屑病斑块皮肤样本中白细胞介素8细胞因子水平升高。我们得出结论，移植到严重联合免疫缺陷小鼠身上的正常和银屑病皮肤的人类样本在移植前后有许多相似之处。因此，我们认为这种新的动物模型适用于旨在揭示这种重要皮肤疾病潜在的遗传/病因异常以及更好地阐明其病理生理基础的更多机制类型研究。
