Lichter Jutta, Heckelen Angela, Fischer Klaus, Blomeke Brunhilde
Department of Environmental Toxicology, Trier, Germany.
J Toxicol Environ Health A. 2008;71(13-14):960-4. doi: 10.1080/15287390801989135.
Dendritic cells (DCs) are known to internalize, process, and present low-molecular-weight chemicals to T cells in the course of the sensitization and elicitation phase of allergic contact dermatitis. Thus, DCs may be involved in metabolic activation and detoxification of haptens and thereby influence the quantity of immunogens inducing sensitization. Recently, the cytochrome P-450 enzymes expressed in monocyte-derived dendritic cells (MoDCs) were characterized. In the present study, N-acetyltransferase 1 and 2 (NAT-1 and -2) mRNA expression and N-acetylation capacities of these cells were investigated. Monocytes from healthy donors were incubated with granulocyte-monocyte colony-stimulating factor (GM-CSF) and interleukin (IL)-4 for 6 d and the resulting immature MoDCs were characterized by flow cytometry. Total RNA from MoDCs was isolated, reverse transcribed, and polymerase chain reaction (PCR) for NAT-1 and NAT-2 mRNA was performed. Data showed the presence of mRNA for NAT-1 (9 of 10 donors) and NAT-2 (8 of 10 donors) in these cells. NAT-1 enzyme activities were achieved through acetylation of para-aminobenzoic acid (PABA) by MoDC cell lysates and activities varied between 23.4 and 26.6 nmol/mg/min. In addition, complete cell acetylation of para-phenylenediamine (PPD), estimated via analysis of monoacetyl-PPD (MAPPD) and diacetyl-PPD (DAPPD) in cell culture supernatants, confirmed that in vitro generated MoDCs (4 of 6 donors) express metabolic active N-acetyltransferase (NAT-1). In the case of PPD, our results emphasize that N-acetylation status may influence the amounts of immunogens available for sensitization to PPD.
已知树突状细胞(DCs)在过敏性接触性皮炎的致敏和激发阶段会内化、处理低分子量化学物质并将其呈递给T细胞。因此,DCs可能参与半抗原的代谢激活和解毒,从而影响诱导致敏的免疫原数量。最近,单核细胞衍生树突状细胞(MoDCs)中表达的细胞色素P-450酶得到了表征。在本研究中,对这些细胞的N-乙酰转移酶1和2(NAT-1和-2)mRNA表达及N-乙酰化能力进行了研究。将健康供体的单核细胞与粒细胞-单核细胞集落刺激因子(GM-CSF)和白细胞介素(IL)-4孵育6天,通过流式细胞术对产生的未成熟MoDCs进行表征。从MoDCs中分离总RNA,进行逆转录,并对NAT-1和NAT-2 mRNA进行聚合酶链反应(PCR)。数据显示这些细胞中存在NAT-1(10名供体中的9名)和NAT-2(10名供体中的8名)的mRNA。通过MoDC细胞裂解物对对氨基苯甲酸(PABA)进行乙酰化来实现NAT-1酶活性,活性在23.4至26.6 nmol/mg/min之间变化。此外,通过分析细胞培养上清液中的单乙酰对苯二胺(MAPPD)和二乙酰对苯二胺(DAPPD)来估计对苯二胺(PPD)的完全细胞乙酰化,证实体外产生的MoDCs(6名供体中的4名)表达代谢活性N-乙酰转移酶(NAT-1)。对于PPD,我们的结果强调N-乙酰化状态可能影响可用于对PPD致敏的免疫原数量。