Geiselhart L A, Christian T, Minnear F, Freed B M
Department of Microbiology, Immunology and Molecular Genetics, Albany Medical College, New York 12208, USA.
Toxicol Appl Pharmacol. 1997 Mar;143(1):30-6. doi: 10.1006/taap.1996.8071.
Cigarette smoking has been shown to cause profound suppression of T-cell responses in the lungs, but the mechanism by which this phenomenon occurs is not known. We have shown that 10 microM p-benzoquinone (p-BQ), a thiol-reactive benzene derivative found in cigarette tar, inhibits mitogen-induced IL-2 production by human peripheral blood mononuclear cells by 76 +/- 7% without affecting lymphocyte/macrophage agglutination or blast transformation. The effect of p-BQ appeared to be specific for IL-2 production, since de novo induction of the IL-2 receptor alpha-chain (CD25) and ICAM-1 (CD54) and upregulation of LFA-1 alpha/beta (CD11a and CD18) were unaffected. In contrast, N-ethylmaleimide (NEM), another alpha,beta-unsaturated diketone with thiol-reactive properties similar to those of p-BQ, inhibited all of these Con A-induced activation events. These results suggest that p-BQ inhibits T-cell mitogenesis by blocking a thiol-dependent event that controls IL-2 production but not other T-cell activation events.
吸烟已被证明会导致肺部T细胞反应受到显著抑制，但其发生机制尚不清楚。我们发现，香烟焦油中含有的一种硫醇反应性苯衍生物——10微摩尔对苯醌（p-BQ），可抑制人外周血单核细胞由丝裂原诱导的白细胞介素-2（IL-2）产生，抑制率达76±7%，且不影响淋巴细胞/巨噬细胞凝集或母细胞转化。p-BQ的作用似乎对IL-2产生具有特异性，因为IL-2受体α链（CD25）和细胞间黏附分子-1（ICAM-1，CD54）的从头诱导以及淋巴细胞功能相关抗原-1α/β（LFA-1α/β，CD11a和CD18）的上调均未受影响。相比之下，另一种具有与p-BQ类似硫醇反应特性的α,β-不饱和二酮——N-乙基马来酰亚胺（NEM），则抑制了所有这些刀豆蛋白A诱导的激活事件。这些结果表明，p-BQ通过阻断控制IL-2产生但不影响其他T细胞激活事件的硫醇依赖性事件来抑制T细胞有丝分裂。
