Decreased levels of sphingosine, a natural antimicrobial agent, may be associated with vulnerability of the stratum corneum from patients with atopic dermatitis to colonization by Staphylococcus aureus
Decreased levels of sphingosine, a natural antimicrobial agent, may be associated with vulnerability of the stratum corneum from patients with atopic dermatitis to colonization by Staphylococcus aureus
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DOI：
10.1046/j.1523-1747.2002.01846.x
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发表时间：
2002-08-01
影响因子：
6.5
通讯作者：
Imokawa, G
中科院分区：
文献类型：
--
作者：
Arikawa, J;Ishibashi, M;Imokawa, G
特应性皮炎患者皮肤的角质层非常容易被各种细菌定植，包括金黄色葡萄球菌。在特应性皮炎皮肤中，皮肤抵抗细菌入侵的防御系统似乎被显着破坏，但人们对所涉及的防御机制知之甚少。作为一种鞘脂代谢物，鞘氨醇在生理水平上对金黄色葡萄球菌具有有效的抗菌作用，并且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对金黄色葡萄球菌定植的获得性脆弱性有关。在这项研究中，我们测量了特应性皮炎患者上层角质层中的鞘氨醇水平，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的鞘氨醇水平显着下调。鞘氨醇水平的降低与同一受试者上层角质层中细菌数量的增加有关，其中包括金黄色葡萄球菌。这表明特应性皮炎患者体内细菌定植增加可能是由于缺乏作为天然抗菌剂的鞘氨醇所致。至于特应性皮炎中鞘氨醇生成减少的机制，对神经酰胺酶（主要的鞘氨醇产生酶）活性的分析表明，特应性皮炎患者和健康对照者之间碱性神经酰胺酶的活性没有差异，而特应性皮炎患者中酸性神经酰胺酶的活性显着降低，这与特应性皮炎患者的神经酰胺酶活性明显降低有关。 细菌在这些受试者体内定植。此外，同一特应性皮炎患者的角质层上层中的鞘氨醇和酸性神经酰胺酶（r = 0.65，p < 0.01）或神经酰胺（r = 0.70，p < 0.01）水平之间存在密切相关性。总的来说，我们的结果表明，特应性皮炎患者皮肤中细菌定植的脆弱性可能与天然抗菌剂鞘氨醇水平降低有关，这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活性降低所致。
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.