Skin as a route of exposure and sensitization in chronic beryllium disease
Skin as a route of exposure and sensitization in chronic beryllium disease
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DOI：
10.1289/ehp.5999
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发表时间：
2003-07-01
影响因子：
10.4
通讯作者：
Adkins, EJ
中科院分区：
文献类型：
--
作者：
Tinkle, SS;Antonini, JM;Adkins, EJ
慢性铍病是一种职业性肺部疾病，始于对铍的细胞介导的免疫反应。尽管在过去十年中，呼吸和工程控制显著降低了铍的职业暴露，但铍致敏率并未下降。我们假设，皮肤暴露于铍颗粒将提供一种替代途径致敏这种金属。我们采用光学扫描激光共聚焦显微镜和大小选择荧光球，以证明0.5-和1.0-妈妈的颗粒，结合运动，在手腕，穿透人体皮肤的角质层，并达到表皮，偶尔，真皮。对化学致敏剂的皮肤免疫应答在皮肤中起始，在局部淋巴结（LN）中成熟，并将半抗原特异性T细胞释放到外周血中。局部应用铍C3 H小鼠产生铍特异性致敏，记录外周血和LN铍淋巴细胞增殖试验（BeLPT）和LN T细胞活化标志物的变化，增加表达的CD 44，和减少CD 62 L。在致敏-激发治疗范例中，表皮铍在化学激发后增加小鼠耳厚度。这些数据与局部应用铍后半抗原特异性细胞介导的免疫反应的发展一致，并表明铍工人致敏的持续率与皮肤暴露于精细和超细铍颗粒之间存在机械联系。
Chronic beryllium disease is an occupational lung disease that begins as a cell-mediated immune response to beryllium. Although respiratory and engineering controls have significantly decreased occupational beryllium exposures over the last decade, the rate of beryllium sensitization has not declined. We hypothesized that skin exposure to beryllium particles would provide an alternative route for sensitization to this metal. We employed optical scanning laser confocal microscopy and size-selected fluorospheres to demonstrate that 0.5- and 1.0-mum particles, in conjunction with motion, as at the wrist, penetrate the stratum corneum of human skin and reach the epidermis and, occasionally, the dermis. The cutaneous immune response to chemical sensitizers is initiated in the skin, matures in the local lymph node (LN), and releases hapten-specific T cells into the peripheral blood. Topical application of beryllium to C3H mice generated beryllium-specific sensitization that was documented by peripheral blood and LN beryllium lymphocyte proliferation tests (BeLPT) and by changes in LN T-cell activation markers, increased expression of CD44, and decreased CD62L. In a sensitization-challenge treatment paradigm, epicutaneous beryllium increased murine ear thickness following chemical challenge. These data are consistent with development of a hapten-specific, cell-mediated immune response following topical application of beryllium and suggest a mechanistic link between the persistent rate of beryllium worker sensitization and skin exposure to fine and ultrafine beryllium particles.