Menon G K, Elias P M, Feingold K R
Dermatology Service, Veterans Administration Medical Center, San Francisco, CA 94121.
Br J Dermatol. 1994 Feb;130(2):139-47. doi: 10.1111/j.1365-2133.1994.tb02892.x.
Prior studies have demonstrated a Ca2+ gradient within the epidermis, with the highest concentration in the outer nucleated layers, disappearance of the Ca2+ gradient when the permeability barrier is acutely disrupted, and reappearance of the Ca2+ gradient in parallel with barrier repair, and disruption of the gradient in psoriasis. These observations suggest that integrity of the permeability barrier may maintain the epidermal Ca2+ gradient. To determine further whether a functional barrier is crucial for maintaining the Ca2+ gradient, we examined Ca2+ distribution by ion-capture cytochemistry in essential-fatty-acid-deficient (EFAD) and topical-lovastatin-treated mice, which display a chronic barrier abnormality. In both models, loss of the Ca2+ gradient occurred due to increased cytosolic Ca2+ in the lower epidermis, which normally displays a paucity of Ca2+. Moreover, artificial barrier restoration for 48 h with a water vapour-impermeable wrap normalized the Ca2+ distribution pattern. Acute barrier disruption also leads to the loss of the Ca2+ gradient, but in contrast with the chronic models, loss of the gradient was due to decreased Ca2+ in the upper epidermis. Occlusion with a vapour-impermeable wrap blocked restoration of the Ca2+ gradient after acute barrier disruption. These results demonstrate that chronic barrier disruption increases Ca2+ in the epidermis, and blockade of water flux normalizes Ca2+ distribution, whereas acute barrier disruption leads to loss of Ca2+, and blockade of water flux prevents the return of Ca2+. We conclude: (i) that the epidermal Ca2+ reservoir is derived from the movement of fluids and Ca2+ across the basement membrane, and (ii) that the integrity of the permeability barrier maintains the epidermal Ca2+ gradient.
先前的研究已证实表皮内存在钙离子梯度，在外层有核层中浓度最高，当通透性屏障急性受损时钙离子梯度消失，随着屏障修复钙离子梯度重新出现，而在银屑病中该梯度被破坏。这些观察结果表明通透性屏障的完整性可能维持表皮钙离子梯度。为了进一步确定功能性屏障对于维持钙离子梯度是否至关重要，我们通过离子捕获细胞化学方法检测了必需脂肪酸缺乏（EFAD）小鼠和局部用洛伐他汀治疗的小鼠的钙离子分布，这两种小鼠表现出慢性屏障异常。在这两种模型中，钙离子梯度的丧失是由于下表皮细胞质钙离子增加所致，而下表皮正常情况下钙离子含量很少。此外，用不透水汽的包裹物进行48小时的人工屏障修复可使钙离子分布模式恢复正常。急性屏障破坏也会导致钙离子梯度丧失，但与慢性模型不同的是，梯度丧失是由于上表皮钙离子减少。用不透水汽的包裹物封闭可阻止急性屏障破坏后钙离子梯度的恢复。这些结果表明，慢性屏障破坏会增加表皮中的钙离子，而阻断水通量可使钙离子分布恢复正常，而急性屏障破坏会导致钙离子丧失，阻断水通量可阻止钙离子恢复。我们得出以下结论：（i）表皮钙离子库源自液体和钙离子跨基底膜的移动，（ii）通透性屏障 的完整性维持表皮钙离子梯度。
