Experimental Pathology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Dermatology and Venereology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Sci Rep. 2016 Jun 13;6:27890. doi: 10.1038/srep27890.
Ultraviolet (UV) irradiation induces skin pigmentation, which relies on the intercellular crosstalk of melanin between melanocytes to keratinocytes. However, studying the separate effects of UVA and UVB irradiation reveals differences in cellular response. Herein, we show an immediate shedding of extracellular vesicles (EVs) from the plasma membrane when exposing human melanocytes to UVA, but not UVB. The EV-shedding is preceded by UVA-induced plasma membrane damage, which is rapidly repaired by Ca(2+)-dependent lysosomal exocytosis. Using co-cultures of melanocytes and keratinocytes, we show that EVs are preferably endocytosed by keratinocytes. Importantly, EV-formation is prevented by the inhibition of exocytosis and increased lysosomal pH but is not affected by actin and microtubule inhibitors. Melanosome transfer from melanocytes to keratinocytes is equally stimulated by UVA and UVB and depends on a functional cytoskeleton. In conclusion, we show a novel cell response after UVA irradiation, resulting in transfer of lysosome-derived EVs from melanocytes to keratinocytes.
紫外线(UV)照射会引起皮肤色素沉着,这依赖于黑素细胞与角质形成细胞之间的黑色素细胞间相互作用。然而,研究 UVA 和 UVB 照射的单独作用会揭示出细胞反应的差异。在此,我们发现当将人黑素细胞暴露于 UVA 时,会立即从质膜脱落细胞外囊泡(EVs),而不是 UVB。EV 脱落之前是 UVA 诱导的质膜损伤,这迅速被 Ca(2+)-依赖性溶酶体胞吐作用修复。使用黑素细胞和角质形成细胞的共培养物,我们发现 EVs 优先被角质形成细胞内吞。重要的是,通过抑制胞吐作用和增加溶酶体 pH 可以阻止 EV 形成,但不会被肌动蛋白和微管抑制剂影响。黑素体从黑素细胞向角质形成细胞的转移同样受到 UVA 和 UVB 的刺激,并且依赖于功能正常的细胞骨架。总之,我们展示了 UVA 照射后的一种新的细胞反应,导致来自黑素细胞的溶酶体衍生 EV 转移到角质形成细胞。