Ozaki Kiyokazu, Matsuura Tetsuro, Narama Isao
Research Institute of Drug Safety, Setsunan University, Hirakata, Japan.
Int Arch Allergy Immunol. 2005 Jan;136(1):73-82. doi: 10.1159/000082587. Epub 2004 Dec 8.
Atopic dermatitis (AD) is a common skin disease characterized by chronic recurrent eczematous lesions, but its exact etiology and mechanism are unclear. We found that beige rats (DAbg/bg), a mutant model of Chediak-Higashi syndrome, develop skin lesions characterized by pruritus, excoriation, erosion and alopecia. We describe the beige rat and examine its possible usefulness as an AD model.
Beige rats of 4, 8, 13, 16, 26 and 52 weeks were used. Histological analysis of the skin was performed. Plasma IgE and cytokines were measured. Th1 and Th2 cytokines and RANTES mRNA expression of skin and lymph nodes were evaluated. Passive cutaneous anaphylaxis (PCA) reactions were examined, and maximization tests were conducted.
Skin lesions begin to develop with increases in serum IgE levels and the expression of IL-4 mRNA in the lymph node and skin. Histologically, skin lesions are characterized by acanthosis, ulceration and inflammatory cell infiltration in the dermis. Inflammatory cells consist of CD3+, CD4+, ED1+, ED2+ and I-A+ mononuclear cells, eosinophils, degranulated mast cells and neutrophils accompanying interleukin (IL)-4, interferon (IFN)-gamma and RANTES mRNA expressions of the skin. Inflammatory cells are reduced during chronification with decreased expressions of IL-4, IFN-gamma and RANTES mRNA. In addition, the rats show a high sensitivity to PCA reactions and maximization tests.
Our results show that some of the skin lesions of beige rats are morphologically similar to human AD, being characterized by inflammatory cell composition in the acute phase, and increased IgE and RANTES levels. However, the inflammatory process and cytokine expression pattern are different from those in human AD.
特应性皮炎(AD)是一种常见的皮肤病,其特征为慢性复发性湿疹样皮损,但其确切病因和发病机制尚不清楚。我们发现,米色大鼠(DAbg/bg)作为切-东综合征的突变模型,会出现以瘙痒、擦伤、糜烂和脱发为特征的皮肤病变。我们描述了米色大鼠,并探讨其作为AD模型的潜在用途。
使用4周、8周、13周、16周、26周和52周龄的米色大鼠。对皮肤进行组织学分析。检测血浆IgE和细胞因子水平。评估皮肤和淋巴结中Th1和Th2细胞因子以及RANTES mRNA的表达。检测被动皮肤过敏反应(PCA),并进行激发试验。
随着血清IgE水平升高以及淋巴结和皮肤中IL-4 mRNA表达增加,皮肤病变开始出现。组织学上,皮肤病变的特征为棘层肥厚、溃疡形成以及真皮层的炎症细胞浸润。炎症细胞包括CD3+、CD4+、ED1+、ED2+和I-A+单核细胞、嗜酸性粒细胞、脱颗粒肥大细胞以及中性粒细胞,同时伴有皮肤中白细胞介素(IL)-4、干扰素(IFN)-γ和RANTES mRNA的表达。随着病情慢性化,炎症细胞减少,IL-4、IFN-γ和RANTES mRNA的表达也降低。此外,这些大鼠对PCA反应和激发试验表现出高度敏感性。
我们的结果表明,米色大鼠的一些皮肤病变在形态上与人类AD相似,急性期以炎症细胞组成、IgE和RANTES水平升高为特征。然而,其炎症过程和细胞因子表达模式与人类AD不同。