Hylkema M N, Hoekstra M O, Luinge M, Timens W
Department of Pathology and Laboratory Medicine, University Hospital Groningen, The Netherlands.
Clin Exp Immunol. 2002 Sep;129(3):390-6. doi: 10.1046/j.1365-2249.2002.01938.x.
To examine the influence of genetics on the OVA-induced allergic inflammatory response in lungs we compared rats that are genetically Th2-predisposed (Brown Norway, inbred) or not genetically predisposed (Sprague Dawley, outbred). Rats were sensitized with ovalbumin (OVA) and challenged four weeks later with OVA aerosol. Eighteen hours after challenge, lung tissue was studied for evaluation of numbers of eosinophils, neutrophils, macrophages and mast cells, as well as for expression of P-selectin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells. From a separate portion of the pulmonary tissue, leucocytes were isolated to analyse numbers of IFNgamma and IL-4 producing cells (ELISPOT assay) and frequencies of T-cell subsets and B cells. We found increased numbers of eosinophils and neutrophils in the lung, an increased number of IL-4 producing cells in lung cell isolates and increased levels of serum (OVA- specific)-IgE in both rat strains. In addition, expression of E-selectin and ICAM-1 was up regulated in both rat strains whereas expression of VCAM-1 was only up regulated in the BN rat. Although the 'allergic' Th2 response to OVA was detectable in both rat strains, it was more pronounced in the BN rat than in the SD rat. However, the SD rat, which is not predisposed to respond in either a Th2 or Th1-like way, appeared capable of mounting an allergic response to OVA. This suggests that other factors than genetic contribute to allergic disease.
为研究遗传学对卵清蛋白（OVA）诱导的肺部过敏性炎症反应的影响，我们比较了具有Th2倾向的遗传大鼠（近交系棕色挪威大鼠）和无遗传倾向的大鼠（远交系斯普拉格-道利大鼠）。用卵清蛋白（OVA）致敏大鼠，四周后用OVA气雾剂进行激发。激发18小时后，研究肺组织以评估嗜酸性粒细胞、中性粒细胞、巨噬细胞和肥大细胞的数量，以及内皮细胞上P-选择素、E-选择素、细胞间黏附分子-1（ICAM-1）和血管细胞黏附分子-1（VCAM-1）的表达。从肺组织的另一部分分离白细胞，分析产生IFNγ和IL-4的细胞数量（酶联免疫斑点分析）以及T细胞亚群和B细胞的频率。我们发现，两种大鼠品系的肺中嗜酸性粒细胞和中性粒细胞数量增加，肺细胞分离物中产生IL-4的细胞数量增加，血清（OVA特异性）IgE水平升高。此外，两种大鼠品系中E-选择素和ICAM-1的表达均上调，但VCAM-1的表达仅在BN大鼠中上调。尽管在两种大鼠品系中均检测到对OVA的“过敏性”Th2反应，但在BN大鼠中比在SD大鼠中更明显。然而，SD大鼠既没有Th2样反应倾向，也没有Th1样反应倾向，但似乎能够对OVA产生过敏反应。这表明除了遗传因素外，其他因素也会导致过敏性疾病。
