Ackermann L, Harvima I T
Department of Dermatology, University of Kuopio, Finland.
Arch Dermatol Res. 1998 Jul;290(7):353-9. doi: 10.1007/s004030050317.
The release of cytokines from cutaneous cells may be of major importance in the initiation and development of many inflammatory skin disorders. For example, tumor necrosis factor-alpha (TNF-alpha), which in healthy skin is found preformed only in mast cells, is able to induce the expression of several adhesion molecules including intercellular adhesion molecule-1 (ICAM-1). Increased expression of ICAM-1 occurs in keratinocytes in lesional skin of psoriasis and atopic dermatitis (AD) and it is considered to be an important initiator of leucocyte/keratinocyte interactions in skin inflammation. We counted the mast cells showing TNF-alpha immunoreactivity using a double-staining method in nonlesional and lesional skin sections from 12 patients with AD and 12 patients with psoriasis. The percentage of TNF-alpha+ mast cells in lesional and nonlesional AD skin was 36 +/- 22% and 21 +/- 15% (P < 0.018, paired t-test), respectively, and in psoriatic skin was 16 +/- 25% and 15 +/- 15%, respectively (P < 0.89, paired t-test). We also cultured whole skin biopsies taken from the healthy-looking skin of psoriatic and AD patients in the presence of mast cell degranulator compound 48/80, which resulted in focal expression of ICAM-1 in the epidermis. In cultured keratinocytes, both histamine and an extract of a human mast-cell line (HMC-1) induced ICAM-1 immunostaining only in occasional cells, but the combination of histamine and the HMC-1 extract resulted in intense ICAM-1 staining in numerous cells. This enhancement of ICAM-1 staining was abolished by preincubation of the HMC-1 extract with anti-TNF-alpha antibody. These results suggest that the degranulation of mast cells induces the expression of ICAM-1 in keratinocytes probably via TNF-alpha and histamine.
皮肤细胞释放细胞因子在许多炎症性皮肤病的发生和发展中可能起主要作用。例如，肿瘤坏死因子-α（TNF-α）在健康皮肤中仅预先存在于肥大细胞中，它能够诱导包括细胞间粘附分子-1（ICAM-1）在内的几种粘附分子的表达。ICAM-1表达增加出现在银屑病和特应性皮炎（AD）的皮损角质形成细胞中，并且被认为是皮肤炎症中白细胞/角质形成细胞相互作用的重要启动因素。我们使用双染色法对12例AD患者和12例银屑病患者的非皮损和皮损皮肤切片中显示TNF-α免疫反应性的肥大细胞进行计数。AD皮损和非皮损皮肤中TNF-α +肥大细胞的百分比分别为36±22%和21±15%（配对t检验，P < 0.018），银屑病皮肤中分别为16±25%和15±15%（配对t检验，P < 0.89）。我们还在肥大细胞脱颗粒剂化合物48/80存在的情况下培养了取自银屑病和AD患者外观正常皮肤的全层皮肤活检组织，这导致表皮中ICAM-1的局灶性表达。在培养的角质形成细胞中，组胺和人肥大细胞系（HMC-1）提取物仅在偶尔的细胞中诱导ICAM-1免疫染色，但组胺和HMC-1提取物的组合导致许多细胞中ICAM-1染色强烈。用抗TNF-α抗体预孵育HMC-1提取物可消除ICAM-1染色的这种增强。这些结果表明肥大细胞脱颗粒可能通过TNF-α和组胺诱导角质形成细胞中ICAM-1的表达。
