Hayashi Toshiharu, Fujii Taeko
Laboratory of Veterinary Pathology, Faculty of Agriculture, Yamaguchi University, Yamaguchi, Japan.
Int J Exp Pathol. 2008 Jun;89(3):188-200. doi: 10.1111/j.1365-2613.2008.00577.x.
The mechanisms of distant manifestation after a local allergic reaction are largely unknown. This study examined the development of cutaneous lesions in a mouse model of late allergic rhinitis (LAR). BALB/c mice were sensitized by ovalbumin (OVA) intraperitoneally two times (on days 0 and 10) and challenged by OVA intranasally on day 14. Four days after OVA challenge, nasal and cutaneous lesions including helper T (Th) responses, expression of adhesion molecules and presence of OVA and IgE were examined, and compared with unsensitized and unchallenged (control) mice. Compared with the control group, the LAR group developed LAR characterized by infiltration of lymphocytes and eosinophils, increased IgE values and increased productions of IL-4 and IL-5, but not IFN-gamma. A dominant infiltration of eosinophils and increase in mast cells, attachment of eosinophils to endothelium, intense expression of VCAM-1 on endothelium in venules and VLA-4 expression on eosinophils and mast cells were recognized in the cutaneous tissues. There were no differences in the expression of ICAM-1 on vascular endothelium and LFA-1 on infiltrated leucocytes between the two groups. CLA expression on lymphocytes was not detected, and the binding of OVA and IgE on mast cells and eosinophils was found in the cutaneous lesions in the LAR group, but not in the control group. This study suggests that acute urticaria[corrected]-like lesions in OVA-unexposed cutaneous tissues may be induced by immediate allergic reaction due to the systemic development of Th2-type response in a mouse model of LAR.
局部过敏反应后远处表现的机制在很大程度上尚不清楚。本研究在迟发性变应性鼻炎(LAR)小鼠模型中检测了皮肤病变的发展情况。BALB/c小鼠腹腔注射卵清蛋白(OVA)进行两次致敏(分别在第0天和第10天),并于第14天经鼻给予OVA激发。OVA激发后4天,检测鼻和皮肤病变,包括辅助性T(Th)反应、黏附分子表达以及OVA和IgE的存在情况,并与未致敏和未激发(对照)小鼠进行比较。与对照组相比,LAR组发生了以淋巴细胞和嗜酸性粒细胞浸润、IgE值升高以及IL-4和IL-5产生增加为特征的LAR,但IFN-γ未增加。在皮肤组织中观察到嗜酸性粒细胞的显著浸润和肥大细胞的增加、嗜酸性粒细胞与内皮的附着、小静脉内皮上VCAM-1的强烈表达以及嗜酸性粒细胞和肥大细胞上VLA-4的表达。两组之间血管内皮上ICAM-1的表达和浸润白细胞上LFA-1的表达没有差异。未检测到淋巴细胞上CLA的表达,在LAR组的皮肤病变中发现了OVA和IgE与肥大细胞和嗜酸性粒细胞的结合,而对照组中未发现。本研究表明,在LAR小鼠模型中,由于Th2型反应的全身发展,未暴露于OVA的皮肤组织中可能会因即刻过敏反应诱发类似急性荨麻疹样的病变。