Semper Amanda E, Heron Kyle, Woollard Alexander C s, Kochan Jarema P, Friedmann Peter S, Church Martin K, Reischl Ilona G
Division of Infection, Inflammation and Repair, School of Medicine, University of Southampton, United Kingdom.
J Allergy Clin Immunol. 2003 Aug;112(2):411-9. doi: 10.1067/mai.2003.1626.
Fc epsilon RI expressed on the surface of human epidermal Langerhans' cells facilitates uptake of IgE-associated allergens and plays a pivotal role in the pathogenesis of atopic dermatitis. Seminal results from studies investigating Langerhans' cell Fc epsilon RI in skin biopsy sections or epidermal cell suspensions demonstrate the highest receptor expression in lesional skin of patients with active atopic dermatitis.
We sought to investigate and localize Fc epsilon RI expression on Langerhans' cells within a minimally disturbed tissue environment in clinically uninvolved skin and to compare receptor expression between healthy donors and patients with atopic dermatitis or other allergic diseases.
Intact epidermal sheets from skin suction blisters, immunofluorescently stained with Langerhans' cell markers and anti-Fc epsilon RI alpha (mAbs 15E5 and 22E7) or anti-IgE, were examined by means of confocal microscopy. Samples incubated with anti-Fc epsilon RI alpha before or after cell fixation-permeabilization were compared to discriminate between cytoplasmic and membrane localization.
Cytoplasmic Fc epsilon RI alpha chain was found in Langerhans' cells from all donors, irrespective of atopic status. Surface Fc epsilon RI-bound IgE was detected in the skin of individuals with active atopic dermatitis and in the skin of those with active asthma or rhinitis. No surface Fc epsilon RI was expressed in the skin of patients with a clinical history of atopic dermatitis, asthma, or rhinitis whose disease was in remission or in the skin of nonatopic individuals.
In clinically uninvolved skin, Langerhans' cell-surface Fc epsilon RI expression is not only linked to atopic dermatitis but is also generally associated with allergic disease. This supports the concept of a systemic regulatory mechanism associated with active allergic disease, which is further aggravated by local inflammation in atopic skin lesions.
人表皮朗格汉斯细胞表面表达的FcεRI促进与IgE相关的变应原摄取,并在特应性皮炎的发病机制中起关键作用。在皮肤活检切片或表皮细胞悬液中研究朗格汉斯细胞FcεRI的开创性结果表明,在活动性特应性皮炎患者的皮损中受体表达最高。
我们试图在临床未受累皮肤中最小程度受干扰的组织环境中研究和定位朗格汉斯细胞上FcεRI的表达,并比较健康供体与特应性皮炎患者或其他过敏性疾病患者之间的受体表达。
用朗格汉斯细胞标志物和抗FcεRIα(单克隆抗体15E5和22E7)或抗IgE进行免疫荧光染色的皮肤吸引水疱完整表皮片,通过共聚焦显微镜检查。比较在细胞固定-通透处理之前或之后用抗FcεRIα孵育的样品,以区分细胞质和膜定位。
在所有供体的朗格汉斯细胞中均发现细胞质FcεRIα链,与特应状态无关。在活动性特应性皮炎患者的皮肤以及活动性哮喘或鼻炎患者的皮肤中检测到表面FcεRI结合的IgE。在有特应性皮炎、哮喘或鼻炎临床病史且疾病缓解的患者皮肤或非特应个体的皮肤中未表达表面FcεRI。
在临床未受累皮肤中,朗格汉斯细胞表面FcεRI的表达不仅与特应性皮炎有关,而且通常与过敏性疾病有关。这支持了与活动性过敏性疾病相关的全身调节机制的概念,特应性皮肤病变中的局部炎症会进一步加重这种机制。