Okura M, Maeda H, Nishikawa S, Mizoguchi M
Department of Dermatology, St. Marianna University School of Medicine, Kawasaki, Japan.
J Invest Dermatol. 1995 Sep;105(3):322-8. doi: 10.1111/1523-1747.ep12319939.
Previous studies indicate that c-Kit is required for postnatal melanocyte development. To understand the precise mechanisms of c-Kit dependence, we studied melanocyte development in newborn C57BL/6 mice by means of peritoneal injection of a monoclonal anti-c-Kit antibody (ACK2), which blocks c-Kit functions. The mice were injected once or more with ACK2 at various intervals after birth. In experiment 1, skin samples were examined on day 10 post-partum and in experiment 2 they were examined daily until day 10 post-partum. We studied melanocytes in the hair follicles, epidermis, and dermis by light and electron microscopy with dopa reactions and immunohistochemistry. Epidermal melanocytes in untreated mice were dopa negative and c-Kit positive on day 0 post-partum but became dopa positive soon thereafter. In ACK2-treated mice, the earlier the mice received ACK2 injections after birth, the fewer melanocytes they had, not only in the epidermis, but also in follicles. In these mice, melanocytes that had undergone apoptosis in the dermis and the follicles were detected ultrastructurally. Some appeared to have produced tyrosinase, because they had dopa-positive melanosomes. These results suggest that melanocytes in newborn mice are c-Kit dependent and undergo apoptosis when c-Kit receptors are blocked by ACK2 in the early days after birth. During this c-Kit-dependent period, melanocytes differentiate from dopa negative to positive and migrate from the epidermis to hair follicles.
先前的研究表明，c-Kit是出生后黑素细胞发育所必需的。为了了解c-Kit依赖性的确切机制，我们通过腹腔注射阻断c-Kit功能的单克隆抗c-Kit抗体（ACK2），研究了新生C57BL/6小鼠的黑素细胞发育。在出生后的不同时间间隔，给小鼠注射一次或多次ACK2。在实验1中，在产后第10天检查皮肤样本，在实验2中，每天检查直至产后第10天。我们通过多巴反应和免疫组织化学的光镜和电镜研究了毛囊、表皮和真皮中的黑素细胞。未处理小鼠的表皮黑素细胞在产后第0天多巴阴性且c-Kit阳性，但此后不久变为多巴阳性。在接受ACK2处理的小鼠中，出生后越早接受ACK2注射，其黑素细胞越少，不仅在表皮中，在毛囊中也是如此。在这些小鼠中，通过超微结构检测到真皮和毛囊中发生凋亡的黑素细胞。一些似乎产生了酪氨酸酶，因为它们有多巴阳性的黑素小体。这些结果表明，新生小鼠中的黑素细胞依赖c-Kit，并且在出生后早期当c-Kit受体被ACK2阻断时会发生凋亡。在这个依赖c-Kit的时期，黑素细胞从多巴阴性分化为阳性，并从表皮迁移到毛囊。
