Grimbaldeston Michele A, Skov Lone, Finlay-Jones John J, Hart Prue H
Department of Microbiology and Infectious Diseases, School of Medicine, Flinders University, Adelaide, Australia.
Methods. 2002 Sep;28(1):90-6. doi: 10.1016/s1046-2023(02)00213-x.
Exposure to ultraviolet B (UVB) radiation (280-320 nm) is the primary etiologic factor associated with the development of basal cell carcinoma (BCC). The outgrowth of these keratinocyte-derived skin lesions is enhanced by the ability of UVB to impair an immune response that would otherwise eliminate them. Studies in a range of inbred mouse strains as well as mast cell-depleted mice reconstituted with mast cell precursors support a functional link between histamine-staining dermal mast cells and the extent of susceptibility to UVB-induced systemic immunomodulation. Humans, like mouse strains, display variations in dermal mast cell prevalence. In a study of Danish and South Australian BCC patients and control subjects, one 4-mm punch biopsy of non-sun-exposed buttock skin was sampled from each participant. This skin site was investigated to avoid any changes in mast cell prevalence caused by sun exposure. Two sections (4 microm) per biopsy were immunohistochemically stained for detection of histamine-containing dermal mast cells. Computer-generated image analysis evaluated dermal mast cell prevalence in both sections by quantifying the total number of mast cells according to the total dermal area (expressed as mast cells per square millimeter). This technique enabled us to detect heterogeneity of dermal mast cell prevalence in buttock skin between individuals and provided evidence of an association between high dermal mast cell prevalence and BCC development in two diverse populations. We hypothesize that mast cells function in humans, as in mouse strains, by initiating immunosuppression following UV irradiation and, thereby, allowing a permissive environment for the development of BCC. Thus, a high dermal mast cell prevalence as demonstrable in buttock skin is a significant predisposing factor for development of BCC in humans.
暴露于紫外线B（UVB）辐射（280 - 320纳米）是与基底细胞癌（BCC）发生相关的主要病因。UVB损害免疫反应（否则该免疫反应会清除这些病变）的能力增强了这些源自角质形成细胞的皮肤病变的生长。对一系列近交系小鼠以及用肥大细胞前体重建的肥大细胞缺失小鼠的研究支持了组胺染色的真皮肥大细胞与对UVB诱导的全身免疫调节易感性程度之间的功能联系。与小鼠品系一样，人类的真皮肥大细胞患病率也存在差异。在一项针对丹麦和南澳大利亚BCC患者及对照受试者的研究中，从每位参与者非阳光暴露的臀部皮肤取一块4毫米的打孔活检组织。选择该皮肤部位进行研究是为了避免阳光暴露导致的肥大细胞患病率变化。对每份活检组织的两个切片（4微米）进行免疫组织化学染色，以检测含组胺的真皮肥大细胞。计算机生成的图像分析通过根据真皮总面积量化肥大细胞总数（以每平方毫米肥大细胞数表示）来评估两个切片中的真皮肥大细胞患病率。这项技术使我们能够检测个体之间臀部皮肤真皮肥大细胞患病率的异质性，并为两个不同人群中真皮肥大细胞高患病率与BCC发生之间的关联提供了证据。我们假设，与小鼠品系一样，人类肥大细胞的功能是在紫外线照射后启动免疫抑制，从而为BCC的发生创造一个宽松的环境。因此，如在臀部皮肤中所证实的真皮肥大细胞高患病率是人类发生BCC的一个重要易感因素。
