Leigh I M, Navsaria H, Purkis P E, McKay I A, Bowden P E, Riddle P N
ICRF Skin Tumour Laboratory, London, UK.
Br J Dermatol. 1995 Oct;133(4):501-11. doi: 10.1111/j.1365-2133.1995.tb02696.x.
Keratinocyte differentiation in psoriasis was examined using a panel of monospecific monoclonal antibodies to keratins (K), including two recently developed monoclonal antibodies raised to carboxy terminal peptides of K6 (LL020) and K16 (LL025). Keratinocytes from normal skin, untreated psoriatic plaques and non-lesional psoriatic skin, were cultured using multiple in vitro systems. Time-lapse cinephotography was used to measure the intermitotic time of normal and psoriatic keratinocytes in both low calcium-defined and serum-containing media. The intermitotic time did not differ significantly between psoriatic and normal keratinocytes. Keratin expression of psoriatic and normal keratinocytes in vitro was examined by both gel electrophoresis and immunocytochemistry. K6, K16 and K17 were detected suprabasally in all culture systems in vitro, but only in interfollicular psoriatic epidermis in vivo, and not in normal skin. Small subpopulations of keratinocytes expressed simple epithelial keratins K7, K8, K18 and K19 in cultures on plastic substrates, but these keratins were absent in skin equivalents of normal or psoriatic skin. No psoriasis-specific pattern of differentiation was found in vitro. As the K6 peptide antibody reacted with basal cells of normal skin, probably due to K5 cross-reactivity, K16 expression determined by LL025 was found to be the most sensitive indicator of the psoriatic state of differentiation, and this antibody is recommended for future work on psoriasis. K17 had a distinct pattern of tissue distribution in normal skin: K17, but not K16, was present in basal myoepithelial cells in sweat glands, and the deep outer root sheath, but K17 distribution paralleled that of K16 in suprabasal psoriatic epidermis. As keratins K6, K16 and K17 are expressed in keratinocyte hyperproliferation, when high levels of certain cytokines are also expressed, the role of growth factors and regulatory nuclear transcription factors in the control of K6, K16 and K17 expression in psoriasis requires further study, in order to provide insight into the relationship between proliferation and differentiation.
使用一组针对角蛋白（K）的单特异性单克隆抗体，包括最近开发的两种针对K6（LL020）和K16（LL025）羧基末端肽的单克隆抗体，对银屑病中的角质形成细胞分化进行了研究。来自正常皮肤、未经治疗的银屑病斑块和非皮损性银屑病皮肤的角质形成细胞，使用多种体外系统进行培养。采用延时电影摄影术来测量正常和银屑病角质形成细胞在低钙限定培养基和含血清培养基中的分裂间期时间。银屑病角质形成细胞和正常角质形成细胞之间的分裂间期时间没有显著差异。通过凝胶电泳和免疫细胞化学检查了体外培养的银屑病和正常角质形成细胞的角蛋白表达。在所有体外培养系统中，K6、K16和K17在基底层以上被检测到，但仅在体内毛囊间银屑病表皮中被检测到，而在正常皮肤中未被检测到。在塑料基质上培养的角质形成细胞小亚群表达简单上皮角蛋白K7、K8、K18和K19，但在正常或银屑病皮肤的皮肤替代物中不存在这些角蛋白。在体外未发现银屑病特异性的分化模式。由于K6肽抗体与正常皮肤的基底细胞反应，可能是由于K5交叉反应，发现由LL025确定的K16表达是银屑病分化状态最敏感的指标，并且该抗体推荐用于未来关于银屑病的研究。K17在正常皮肤中有独特的组织分布模式：K17而非K16存在于汗腺的基底肌上皮细胞和外根鞘深层，但在基底层以上的银屑病表皮中，K17的分布与K16平行。由于角蛋白K6、K16和K17在角质形成细胞过度增殖时表达，同时也表达高水平的某些细胞因子，因此生长因子和调节性核转录因子在银屑病中控制K6、K16和K17表达中的作用需要进一步研究，以便深入了解增殖与分化之间的关系。
