UNESP - Universidade Estadual Paulista, Laboratório de Imunomorfologia, Departamento de Biologia, São José do Rio Preto, São Paulo, Brazil.
UNIFESP - Universidade Federal de São Paulo, Laboratório de Histologia, Departamento de Morfologia e Genética, São Paulo, Brazil.
Invest Ophthalmol Vis Sci. 2015 Jan 8;56(2):693-704. doi: 10.1167/iovs.14-15100.
Galectin (Gal)-1, a lectin found at sites of immune privilege with critical role in the inflammation, has been poorly investigated in the ocular inflammatory diseases. Here, we evaluated the therapeutic potential of Gal-1 in ocular allergy using a model of ovalbumin (OVA)-induced AC.
OVA-immunized BALB/c male mice were challenged with eye drops containing OVA on days 14 through 16 with a subset of animals pretreated intraperitoneally with recombinant Gal-1 (rGal-1) or dexamethasone (Dex).
Recombinant Gal-1 and Dex administration on days 14 through 16 was effective in reducing the clinical signs of allergic conjunctivitis (AC), plasma anti-OVA IgE levels, Th2 (IL-4 and IL-13), and eotaxin/RANTES levels in the lymph nodes. Four hours after the last OVA challenge, rGal-1 markedly increased Gal-1 endogenous levels in the conjunctiva, and provoked eosinophilia, which persisted at 24 hours. Recombinant Gal-1 had no effect on eosinophil activation, as evidenced by the similar pattern of peroxidase eosinophil expression between cells of rGal-1-treated and untreated AC groups. Conjunctival migrated eosinophils and neutrophils exhibited high levels of Gal-1 and β2-integrin, with points of colocalization, in the rGal-1-treated groups. These different effects observed for rGal-1 were correlated with elevated levels of activated ERK and p38 at 4 hours, and diminished levels of activated JNK and p38 at 24 hours in the eyes.
Gal-1 has an important role in ocular allergic inflammation and represents a potential target for the development of new therapeutic strategies in eye diseases.
半乳糖凝集素（Gal）-1 是一种在免疫特权部位发现的凝集素，在炎症中具有关键作用，但在眼部炎症性疾病中的研究甚少。本研究旨在通过卵清蛋白（OVA）诱导的过敏性结膜炎（AC）模型评估 Gal-1 在眼部过敏中的治疗潜力。
将 OVA 免疫的 BALB/c 雄性小鼠用含有 OVA 的眼药水滴眼，在第 14 天至第 16 天进行眼部挑战，部分动物在腹腔内预先给予重组 Gal-1（rGal-1）或地塞米松（Dex）。
在第 14 天至第 16 天给予 rGal-1 和 Dex 治疗可有效减轻过敏性结膜炎（AC）的临床症状、眼内的血浆抗 OVA IgE 水平、Th2（IL-4 和 IL-13）和嗜酸性粒细胞趋化因子/调节激活正常 T 细胞表达分泌因子（eotaxin/RANTES）水平。在最后一次 OVA 挑战后 4 小时，rGal-1 可显著增加结膜中的内源性 Gal-1 水平，并引起嗜酸性粒细胞增多，该现象在 24 小时时仍持续存在。rGal-1 对嗜酸性粒细胞的激活没有影响，因为 rGal-1 治疗和未治疗的 AC 组细胞中的过氧化物酶嗜酸性粒细胞表达模式相似。在 rGal-1 治疗组中，结膜移行的嗜酸性粒细胞和中性粒细胞表现出高表达 Gal-1 和β2-整合素，并存在共定位现象。rGal-1 观察到的这些不同作用与在眼部 4 小时时 ERK 和 p38 的激活水平升高以及 JNK 和 p38 的激活水平降低有关。
Gal-1 在眼部过敏性炎症中具有重要作用，是眼部疾病新治疗策略发展的潜在靶点。
