Kuper C Frieke, Stierum Rob H, Boorsma Andre, Schijf Marcel A, Prinsen Menk, Bruijntjes Joost P, Bloksma Nanne, Arts Josje H E
TNO, Quality of Life, Zeist, The Netherlands.
Toxicology. 2008 Apr 18;246(2-3):213-21. doi: 10.1016/j.tox.2008.01.013. Epub 2008 Feb 2.
All LMW respiratory allergens known to date can also induce skin allergy in test animals. The question here was if in turn skin allergens can induce allergy in the respiratory tract. Respiratory allergy was tested in Th2-prone Brown Norway (BN) rats by dermal sensitization with the contact allergen dinitrochlorobenzene (DNCB; 1%, day 0; 0.5%, day 7) and a head/nose-only inhalation challenge of 27mg/m3 of DNCB (15 min, day 21), using a protocol that successfully identified chemical respiratory allergens. Skin allergy to DNCB was examined in BN rats and Th1-prone Wistar rats in a local lymph node assay followed by a topical patch challenge of 0.1% DNCB. Sensitization of BN rats via the skin induced DNCB-specific IgG in serum, but not in all animals, and an increased number of CD4+ cells in the lung parenchyma. Subsequent inhalation challenge with DNCB did not provoke apneas or allergic inflammation (signs of respiratory allergy) in the BN rats. However, microarray analysis of mRNA isolated from the lung revealed upregulation of the genes for Ccl2 (MCP-1), Ccl4 (MIP-1beta), Ccl7 and Ccl17. Skin challenge induced considerably less skin irritation and allergic dermatitis in the BN rat than in the Wistar rat. In conclusion, the Th2-prone BN rat appeared less sensitive to DNCB than the Wistar rat; nevertheless, DNCB induced allergic inflammation in the skin of BN rats but even a relatively high challenge concentration did not induce allergy in the respiratory tract, although genes associated with allergy were upregulated in lung tissue.
迄今所知的所有低分子量呼吸道过敏原在实验动物中也可诱发皮肤过敏。这里的问题是,皮肤过敏原反过来是否能诱发呼吸道过敏。通过用接触性过敏原二硝基氯苯(DNCB;1%,第0天;0.5%,第7天)对Th2倾向的棕色挪威(BN)大鼠进行皮肤致敏,并在第21天进行27mg/m³ DNCB的仅头部/鼻部吸入激发(15分钟),采用一种成功鉴定化学呼吸道过敏原的方案,对呼吸道过敏进行了检测。在局部淋巴结试验中对BN大鼠和Th1倾向的Wistar大鼠检测其对DNCB的皮肤过敏,随后进行0.1% DNCB的局部贴片激发。通过皮肤对BN大鼠进行致敏可在血清中诱导产生DNCB特异性IgG,但并非在所有动物中都能诱导产生,并且肺实质中CD4⁺细胞数量增加。随后对BN大鼠进行DNCB吸入激发未引发呼吸暂停或过敏性炎症(呼吸道过敏的迹象)。然而,对从肺中分离的mRNA进行微阵列分析发现,Ccl2(MCP - 1)、Ccl4(MIP - 1β)、Ccl7和Ccl17的基因上调。皮肤激发在BN大鼠中引起的皮肤刺激和过敏性皮炎比在Wistar大鼠中少得多。总之,Th2倾向的BN大鼠对DNCB的敏感性似乎低于Wistar大鼠;尽管如此,DNCB在BN大鼠皮肤中诱导了过敏性炎症,但即使是相对较高的激发浓度也未在呼吸道中诱导过敏,尽管与过敏相关的基因在肺组织中上调。