Griffiths C E, Nickoloff B J
Department of Dermatology, University of Michigan Medical School, Ann Arbor.
Am J Pathol. 1989 Dec;135(6):1045-53.
The ability of small molecules such as urushiol, present as a wax on the poison ivy leaf surface, to cause allergic contact dermatitis (rhus dermatitis) has fascinated immunologists for decades. Current dogma suggests that these epicutaneously applied catechol-containing molecules serve as haptens to conjugate with larger proteins via reactive o-quinone intermediates. These complexes are then recognized as foreign antigens by the immune system and elicit a hypersensitivity reaction. Phorbol ester can directly induce cultured keratinocyte (KC) intercellular adhesion molecule-1 (ICAM-1) expression via a protein kinase C (PK-C)-dependent mechanism. As urushiol is also a known PK-C agonist, we asked if topical application of a poison ivy/oak mixture could directly induce epidermal KC ICAM-1 expression. During the pre-erythematous phase of this reaction (4 to 20 hours), epidermal KCs expressed ICAM-1; this "initiation phase" preceded the appearance of activated memory T lymphocytes in the papillary dermis, and thus appeared to be nonlymphokine mediated. A near-contiguous cellular-adhesion molecular network was identified by ICAM-1 staining of basal KCs, dermal dendrocytes, and endothelial cells. During the second 24-hour period with the onset of erythema and edema, there was an "amplification phase" of more intense KC ICAM-1 expression coupled with relatively weak KC HLA-DR expression that coincided with dermal and epidermal T-cell infiltration. This suggests the presence of lymphokines, such as gamma interferon, during the amplification phase because of KC HLA-DR expression. On cultured KCs, urushiol directly induced ICAM-1 expression but not HLA-DR. Thus, in addition to functioning as an antigenic hapten, urushiol directly induces KC ICAM-1 expression. The KC ICAM-1 expression may then alter the dynamic trafficking of memory T cells in the epidermis, so as to initiate cutaneous inflammation in a nonantigen specific manner. This initiation phase is followed by T-cell infiltration and consequent lymphokine production that significantly amplifies the original stimulus. Thus much can still be learned about the molecular pathophysiology of this common type of cutaneous inflammation.
诸如漆酚（以蜡质形式存在于毒葛叶表面）等小分子引发过敏性接触性皮炎（漆树皮炎）的能力，几十年来一直吸引着免疫学家。当前的理论认为，这些经皮应用的含儿茶酚分子作为半抗原，通过反应性邻醌中间体与更大的蛋白质结合。然后这些复合物被免疫系统识别为外来抗原，并引发超敏反应。佛波酯可通过蛋白激酶C（PK-C）依赖性机制直接诱导培养的角质形成细胞（KC）细胞间黏附分子-1（ICAM-1）表达。由于漆酚也是一种已知的PK-C激动剂，我们探究了局部应用毒葛/橡树混合物是否能直接诱导表皮KC ICAM-1表达。在该反应的红斑前期（4至20小时），表皮KC表达ICAM-1；这个“起始阶段”先于乳头真皮中活化记忆T淋巴细胞的出现，因此似乎是非细胞因子介导的。通过对基底KC、真皮树突状细胞和内皮细胞进行ICAM-1染色，鉴定出一个近乎连续的细胞黏附分子网络。在出现红斑和水肿的第二个24小时期间，存在一个“放大阶段”，此时KC ICAM-1表达更强烈，同时KC HLA-DR表达相对较弱，这与真皮和表皮T细胞浸润同时发生。这表明在放大阶段存在细胞因子，如γ干扰素，因为KC表达HLA-DR。在培养的KC上，漆酚直接诱导ICAM-1表达，但不诱导HLA-DR表达。因此，漆酚除了作为抗原性半抗原发挥作用外，还直接诱导KC ICAM-1表达。KC ICAM-1表达可能会改变记忆T细胞在表皮中的动态运输，从而以非抗原特异性方式引发皮肤炎症。这个起始阶段之后是T细胞浸润以及随之而来的细胞因子产生，这会显著放大原始刺激。因此，关于这种常见类型皮肤炎症的分子病理生理学，仍有很多有待了解。
