Fukuda Ken, Ohbayashi Masaharu, Morohoshi Kei, Zhang Lane, Liu Fu-Tong, Ono Santa J
Department of Ophthalmology, Emory University School of Medicine, Atlanta, Ga., USA.
J Allergy Clin Immunol. 2009 Oct;124(4):827-33.e2. doi: 10.1016/j.jaci.2009.06.012. Epub 2009 Aug 5.
Allergic conjunctivitis is characterized by allergen-specific IgE in the serum and infiltration of eosinophils into the conjunctiva. The role of IgE and mast cells in allergic conjunctivitis is largely unknown, however.
We investigated the importance of conjunctival mast cells in a murine model of IgE-mediated allergic conjunctivitis.
IgE-mediated allergic conjunctivitis was initiated in C57BL/6-Kit(+/+) wild-type mice, mast cell-deficient Kit(W-sh/W-sh) mice, and Kit(W-sh/W-sh) mice that had been subconjunctivally or systemically engrafted with bone marrow-derived, cultured mast cells (BMCMCs) from Kit(+/+) wild-type mice, and clinical symptoms and infiltration of eosinophil of the eyes were evaluated. Total numbers of mast cells in the conjunctiva were counted, and the phenotypes of these cells were characterized by means of immunostaining and PCR analysis of murine mast cell proteases.
No mast cells were detected in the conjunctiva or eyelid dermis of adult Kit(W-sh/W-sh) mice. Subconjunctival injection of BMCMCs resulted in local mast cell reconstitution, with the numbers of reconstituted mast cells in the conjunctiva and eyelid dermis comparable with those observed in wild-type Kit(+/+) littermates. Reconstituted and naive conjunctival mast cells expressed proteases ascribed to connective tissue-type mast cells but not mucosal mast cells. Passive transfer of ragweed-specific IgE followed by antigen challenge resulted in both early-phase clinical symptoms and late-phase eosinophilic inflammation in Kit(+/+) mice. These responses, which were significantly decreased in Kit(W-sh/W-sh) mice, were restored on reconstitution of the conjunctival mast cell population.
These results suggest a direct contribution of IgE-activated mast cells to both the early-phase reaction and late-phase inflammation during ocular allergy.
过敏性结膜炎的特征是血清中存在变应原特异性IgE以及嗜酸性粒细胞浸润至结膜。然而，IgE和肥大细胞在过敏性结膜炎中的作用很大程度上尚不清楚。
我们在IgE介导的过敏性结膜炎小鼠模型中研究结膜肥大细胞的重要性。
在C57BL/6-Kit(+/+)野生型小鼠、肥大细胞缺陷型Kit(W-sh/W-sh)小鼠以及经结膜下或全身移植来自Kit(+/+)野生型小鼠的骨髓来源培养肥大细胞（BMCMC）的Kit(W-sh/W-sh)小鼠中引发IgE介导的过敏性结膜炎，并评估眼部的临床症状和嗜酸性粒细胞浸润情况。对结膜中的肥大细胞总数进行计数，并通过免疫染色和小鼠肥大细胞蛋白酶的PCR分析来鉴定这些细胞的表型。
在成年Kit(W-sh/W-sh)小鼠的结膜或眼睑真皮中未检测到肥大细胞。结膜下注射BMCMC导致局部肥大细胞重建，结膜和眼睑真皮中重建的肥大细胞数量与野生型Kit(+/+)同窝小鼠中观察到的数量相当。重建的和未处理的结膜肥大细胞表达属于结缔组织型肥大细胞而非黏膜肥大细胞的蛋白酶。在给予豚草特异性IgE后进行抗原激发，Kit(+/+)小鼠出现早期临床症状和晚期嗜酸性炎症。这些反应在Kit(W-sh/W-sh)小鼠中显著降低，但在结膜肥大细胞群体重建后得以恢复。
这些结果表明IgE激活的肥大细胞对眼部过敏期间的早期反应和晚期炎症有直接作用。
