Virador V, Matsunaga N, Matsunaga J, Valencia J, Oldham R J, Kameyama K, Peck G L, Ferrans V J, Vieira W D, Abdel-Malek Z A, Hearing V J
Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Pigment Cell Res. 2001 Aug;14(4):289-97. doi: 10.1034/j.1600-0749.2001.140410.x.
Multiple factors affect skin pigmentation, including those that regulate melanocyte and/or keratinocyte function. Such factors, particularly those that operate at the level of the melanosome, are relatively well characterized in mice, but the expression and function of structural and enzymatic proteins in melanocytes in human skin are not as well known. Some years ago, we generated peptide-specific antibodies to murine melanosomal proteins that proved to be instrumental in elucidating melanocyte development and differentiation in mice, but cross-reactivity of those antibodies with the corresponding human proteins often was weak or absent. In an effort to characterize the roles of melanosomal proteins in human skin pigmentation, and to understand the underlying mechanism(s) of abnormal skin pigmentation, we have now generated polyclonal antibodies against the human melanocyte-specific markers, tyrosinase, tyrosinase-related protein (TYRP1), Dopachrome tautomerase (DCT) and Pmel17 (SILV, also known as GP100). We used these antibodies to determine the distribution and function of melanosomal proteins in normal human skin (adult and newborn) and in various cutaneous pigmented lesions, such as intradermal nevi, lentigo simplex, solar lentigines and malignant melanomas. We also examined cytokeratin expression in these same samples to assess keratinocyte distribution and function. Immunohistochemical staining reveals distinct patterns of melanocyte distribution and function in normal skin and in various types of cutaneous pigmented lesions. Those differences in the expression patterns of melanocyte markers provide important clues to the roles of melanocytes in normal and in disrupted skin pigmentation.
多种因素影响皮肤色素沉着，包括那些调节黑素细胞和/或角质形成细胞功能的因素。这类因素，尤其是那些在黑素小体水平起作用的因素，在小鼠中已有相对充分的研究，但人类皮肤黑素细胞中结构蛋白和酶蛋白的表达及功能尚不十分清楚。几年前，我们制备了针对小鼠黑素小体蛋白的肽特异性抗体，这些抗体在阐明小鼠黑素细胞的发育和分化方面发挥了重要作用，但这些抗体与相应人类蛋白的交叉反应性往往较弱或不存在。为了明确黑素小体蛋白在人类皮肤色素沉着中的作用，并了解皮肤色素沉着异常的潜在机制，我们现已制备了针对人类黑素细胞特异性标志物酪氨酸酶、酪氨酸酶相关蛋白（TYRP1）、多巴色素互变异构酶（DCT）和Pmel17（SILV，也称为GP100）的多克隆抗体。我们使用这些抗体来确定黑素小体蛋白在正常人类皮肤（成人和新生儿）以及各种皮肤色素沉着病变（如皮内痣、单纯性雀斑样痣、日光性雀斑样痣和恶性黑色素瘤）中的分布和功能。我们还检测了这些相同样本中的细胞角蛋白表达，以评估角质形成细胞的分布和功能。免疫组织化学染色揭示了正常皮肤和各种类型皮肤色素沉着病变中黑素细胞分布和功能的不同模式。黑素细胞标志物表达模式的这些差异为黑素细胞在正常和紊乱皮肤色素沉着中的作用提供了重要线索。
