Arikawa Junko, Ishibashi Mutsumi, Kawashima Makoto, Takagi Yutaka, Ichikawa Yoshiaki, Imokawa Genji
Department of Dermatology, Tokyo Women's Medical University, Tokyo, Japan; Kao Biological Science Laboratories, Tochigi, Japan.
J Invest Dermatol. 2002 Aug;119(2):433-9. doi: 10.1046/j.1523-1747.2002.01846.x.
The stratum corneum of the skin of patients with atopic dermatitis is highly susceptible to colonization by various bacteria, including Staphylococcus aureus. The defense system of the skin against bacterial invasion appears to be significantly disrupted in atopic dermatitis skin, but little is known about the defense mechanism(s) involved. As one sphingolipid metabolite, sphingosine is known to exert a potent antimicrobial effect on S. aureus at physiologic levels, and it may play a significant role in bacterial defense mechanisms of healthy normal skin. Because of the altered ceramide metabolism in atopic dermatitis, the possible alteration of sphingosine metabolism might be associated with the acquired vulnerability to colonization by S. aureus in patients with atopic dermatitis. In this study, we measured the levels of sphingosine in the upper stratum corneum from patients with atopic dermatitis, and then compared that with the colonization levels of bacteria in the same subjects. Levels of sphingosine were significantly downregulated in uninvolved and in involved stratum corneum of patients with atopic dermatitis compared with healthy controls. This decreased level of sphingosine was relevant to the increased numbers of bacteria including S. aureus present in the upper stratum corneum from the same subjects. This suggests the possibility that the increased colonization of bacteria found in patients with atopic dermatitis may result from a deficiency of sphingosine as a natural antimicrobial agent. As for the mechanism involved in the decreased production of sphingosine in atopic dermatitis, analysis of the activities of ceramidases, major sphingosine-producing enzymes, revealed that, whereas the activity of alkaline ceramidase did not differ between patients with atopic dermatitis and healthy controls, the activity of acid ceramidase was significantly reduced in patients with atopic dermatitis and this had obvious relevance to the increased colonization of bacteria in those subjects. Further, there was a close correlation between the level of sphingosines and acid ceramidase (r = 0.65, p < 0.01) or ceramides (r = 0.70, p < 0.01) in the upper stratum corneum from the same patients with atopic dermatitis. Collectively, our results suggest the possibility that vulnerability to bacterial colonization in the skin of patients with atopic dermatitis is associated with reduced levels of a natural antimicrobial agent, sphingosine, which results from decreased levels of ceramides as a substrate and from diminished activities of its metabolic enzyme, acid ceramidase.
特应性皮炎患者皮肤的角质层极易被包括金黄色葡萄球菌在内的各种细菌定植。在特应性皮炎皮肤中，皮肤抵御细菌入侵的防御系统似乎受到了显著破坏，但对于其中涉及的防御机制却知之甚少。作为一种鞘脂代谢产物，鞘氨醇在生理水平上已知对金黄色葡萄球菌具有强大的抗菌作用，并且它可能在健康正常皮肤的细菌防御机制中发挥重要作用。由于特应性皮炎中神经酰胺代谢的改变，鞘氨醇代谢的可能改变可能与特应性皮炎患者获得性的对金黄色葡萄球菌定植的易感性有关。在本研究中，我们测量了特应性皮炎患者角质层上层中鞘氨醇的水平，然后将其与同一受试者中细菌的定植水平进行比较。与健康对照相比，特应性皮炎患者未受累和受累角质层中鞘氨醇水平均显著下调。鞘氨醇水平的降低与同一受试者角质层上层中包括金黄色葡萄球菌在内的细菌数量增加有关。这表明特应性皮炎患者中发现的细菌定植增加可能是由于作为天然抗菌剂的鞘氨醇缺乏所致。至于特应性皮炎中鞘氨醇产生减少所涉及的机制，对主要的鞘氨醇产生酶神经酰胺酶的活性分析表明，虽然特应性皮炎患者和健康对照之间碱性神经酰胺酶的活性没有差异，但特应性皮炎患者酸性神经酰胺酶的活性显著降低，并且这与这些受试者中细菌定植的增加明显相关。此外，在同一特应性皮炎患者的角质层上层中，鞘氨醇水平与酸性神经酰胺酶（r = 0.65，p < 0.01）或神经酰胺（r = 0.70，p < 0.01）之间存在密切相关性。总体而言，我们的结果表明，特应性皮炎患者皮肤对细菌定植的易感性可能与天然抗菌剂鞘氨醇水平降低有关，而鞘氨醇水平降低是由于作为底物的神经酰胺水平降低及其代谢酶酸性神经酰胺酶的活性降低所致。
