Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ, United States.
Environmental Health Science, New York Medical College, Valhalla, NY, United States.
Exp Mol Pathol. 2014 Jun;96(3):316-27. doi: 10.1016/j.yexmp.2014.03.002. Epub 2014 Mar 21.
Sulfur mustard (SM) is a bifunctional alkylating agent causing skin inflammation, edema and blistering. A hallmark of SM-induced toxicity is follicular and interfollicular epithelial damage. In the present studies we determined if SM-induced structural alterations in hair follicles and sebaceous glands were correlated with cell damage, inflammation and wound healing. The dorsal skin of hairless mice was treated with saturated SM vapor. One to seven days later, epithelial cell karyolysis within the hair root sheath, infundibulum and isthmus was apparent, along with reduced numbers of sebocytes. Increased numbers of utriculi, some with connections to the skin surface, and engorged dermal cysts were also evident. This was associated with marked changes in expression of markers of DNA damage (phospho-H2A.X), apoptosis (cleaved caspase-3), and wound healing (FGFR2 and galectin-3) throughout pilosebaceous units. Conversely, fatty acid synthase and galectin-3 were down-regulated in sebocytes after SM. Decreased numbers of hair follicles and increased numbers of inflammatory cells surrounding the utriculi and follicular cysts were noted within the wound 3-7 days post-SM exposure. Expression of phospho-H2A.X, cleaved caspase-3, FGFR2 and galectin-3 was decreased in dysplastic follicular epidermis. Fourteen days after SM, engorged follicular cysts which expressed galectin-3 were noted within hyperplastic epidermis. Galectin-3 was also expressed in basal keratinocytes and in the first few layers of suprabasal keratinocytes in neoepidermis formed during wound healing indicating that this lectin is important in the early stages of keratinocyte differentiation. These data indicate that hair follicles and sebaceous glands are targets for SM in the skin.
硫芥(SM)是一种双功能烷化剂,可引起皮肤炎症、水肿和水疱。SM 诱导毒性的一个标志是毛囊和滤泡间上皮损伤。在本研究中,我们确定 SM 是否诱导毛囊和皮脂腺的结构改变与细胞损伤、炎症和伤口愈合有关。无毛小鼠的背部皮肤用饱和 SM 蒸气处理。1 至 7 天后,明显可见发根鞘、漏斗和峡部内的上皮细胞核溶解,同时皮脂腺数量减少。可见更多的外囊,其中一些与皮肤表面相连,并且真皮囊肿充盈。这与整个毛囊单位中 DNA 损伤标志物(磷酸化 H2A.X)、细胞凋亡(cleaved caspase-3)和伤口愈合标志物(FGFR2 和半乳糖凝集素-3)表达的明显变化相关。相反,SM 后皮脂腺中的脂肪酸合酶和半乳糖凝集素-3 下调。在 SM 暴露后 3-7 天,在外囊和滤泡囊肿周围观察到毛囊数量减少和炎症细胞数量增加。在发育不良的滤泡上皮中,磷酸化 H2A.X、cleaved caspase-3、FGFR2 和半乳糖凝集素-3 的表达减少。SM 后 14 天,在增生的表皮中观察到充满半乳糖凝集素-3 的充盈滤泡囊肿。半乳糖凝集素-3 也在伤口愈合过程中形成的新表皮中的基底角质形成细胞和上层角质形成细胞的前几层中表达,表明该凝集素在角质形成细胞分化的早期阶段很重要。这些数据表明毛囊和皮脂腺是皮肤中 SM 的靶标。