Anderson C, Hehr A, Robbins R, Hasan R, Athar M, Mukhtar H, Elmets C A
Department of Dermatology, Case Western Reserve University, University Hospitals of Cleveland, Ohio 44106, USA.
J Immunol. 1995 Oct 1;155(7):3530-7.
Experiments were performed to define the metabolic requirements for induction of contact hypersensitivity to polyaromatic hydrocarbons (PAHs), environmental xenobiotics that are both immunotoxic and carcinogenic. Evidence that conversion of the parent compound to a reactive metabolite was necessary for the development of contact hypersensitivity included the fact 1) that contact hypersensitivity to the polyaromatic hydrocarbon dimethylbenz(a)anthracene (DMBA) only occurred in strains of mice that could metabolize the compound, 2) that among the PAHs, only those that could induce aryl hydrocarbon hydroxylase, the rate-limiting enzyme in the PAH metabolic pathway, were immunogenic, and 3) that inhibitors of PAH metabolism reduced DMBA contact hypersensitivity. Cells from the XS52 Langerhans cell-like dendritic cell line were able to metabolize the PAH benzo(a)pyrene to its diol, quinone, and phenol metabolites. GM-CSF augmented benzo(a)pyrene metabolism in XS52 cells. Finally, in vivo depletion of CD8+, but not CD4+, T cell populations inhibited contact hypersensitivity to DMBA. The implications of these experiments are that at least for some contact allergens, the metabolic status of the host is a key determinant of individual susceptibility to the development of allergic contact dermatitis, and the metabolic pathway of an individual hapten may have ramifications for the T cell subpopulation-CD4 or CD8-that is activated.
进行了实验以确定诱导对多环芳烃（PAHs）产生接触性超敏反应的代谢需求，多环芳烃是具有免疫毒性和致癌性的环境外源性物质。母体化合物转化为反应性代谢物对于接触性超敏反应的发生是必要的，这一证据包括以下事实：1）对多环芳烃二甲基苯并（a）蒽（DMBA）的接触性超敏反应仅发生在能够代谢该化合物的小鼠品系中；2）在多环芳烃中，只有那些能够诱导芳烃羟化酶（多环芳烃代谢途径中的限速酶）的才具有免疫原性；3）多环芳烃代谢抑制剂可降低DMBA接触性超敏反应。XS52朗格汉斯细胞样树突状细胞系的细胞能够将多环芳烃苯并（a）芘代谢为其二醇、醌和酚代谢物。GM-CSF增强了XS52细胞中苯并（a）芘的代谢。最后，体内清除CD8 + 而非CD4 + T细胞群体可抑制对DMBA的接触性超敏反应。这些实验的意义在于，至少对于某些接触性变应原而言，宿主的代谢状态是个体对过敏性接触性皮炎易感性的关键决定因素，并且单个半抗原的代谢途径可能对被激活的T细胞亚群（CD4或CD8）产生影响。
