紅斑性狼瘡是屬於自體免疫疾病的一種，其特徵是病患體內會產生自身抗體去辨識自身器官和組織並攻擊之。嗜中性球細胞外網(neutrophil extracellular trap, NET)是一種細胞死亡的過程中，細胞本身會釋出細胞核物質，如染色質等。已有不少文獻指出不正常的嗜中性球細胞外網及其無法被有效分解等現象在紅斑性狼瘡的致病機轉中扮演著重要的角色。其中半乳糖凝集素3參與在發炎反應中如調控嗜中性球的功能。然而半乳糖凝集素3是否在紅斑性狼瘡致病機轉上扮演角色目前尚不明確。因此我們的研究目的是探討半乳糖凝集素3是否藉由調控NET來影響紅斑性狼瘡的致病原因。我們使用臨床紅斑性狼瘡病人檢體及pristane所誘導的小鼠來建立其疾病模式，並且探討在紅斑性狼瘡中，galectin-3和NET之間潛在的關聯性。從我們實驗結果顯示出，紅斑性狼瘡病人相較於正常人，其外周邊血單核細胞(peripheral blood mononuclear cells)會有比較多的半乳糖凝集素3表現量。另外在誘導人類嗜中性球產生NET中偵測到網狀結構內有較多半乳糖凝集素3表現量。我們發現加入半乳糖凝集素之抑制劑乳糖，會減少嗜中性球產生NET之現象。動物實驗方面，在pristane誘導下，相較於半乳糖凝集素3基因剔除小鼠， C57BL/6 小鼠在肺出血部位有表現量較高的galectin-3及較嚴重的免疫複合物。另外在半乳糖凝集素3基因剔除小鼠尿液中有較少尿蛋白含量，和較少肺出血及發炎細胞浸潤，以及較高的存活率。分別加入脂多醣體於C57BL/6及半乳糖凝集素3基因剔除小鼠的嗜中性白血球中，我們發現NET現象在半乳糖凝集素3基因剔除小鼠並不產生。除此之外，我們藉由西方墨點法檢測，發現半乳糖凝集素3基因剔除小鼠嗜中性球有高表現量的caspase，這個發現可能顯示出galectin-3在抑制caspase訊息傳遞中扮演著重要的角色，並且阻止嗜中性球走向細胞凋亡路徑。總結而論，我們的實驗結果顯示出半乳糖凝集素3可能在紅斑性狼瘡致病機轉中調控嗜中性球細胞外網而扮演重要的角色。

Systemic lupus erythematosus (SLE) is an autoimmune disease, characterized by generation of circulating autoantibodies that target multiple organs. NETosis is a cell death pathway characterized by extrusion of chromatin bound to cytosolic and granular contents like bactericidal DNA-based structures called neutrophil extracellular traps (NETs)(Kaplan and Radic 2012). Accumulating data suggest that aberrant NETs and NET degradation play roles in the pathogenesis of SLE. Galectin-3, a member of a family of β-galactoside-binding animal lectins, is involved in many inflammatory responses, including modulation of the functions of neutrophil functions. However, whether galectin-3 contributes to the SLE pathogenesis remains unclear. The aim of this study was to investigate whether galectin-3 impacts NETosis and thereby contributes to the pathogenesis of SLE. We used clinical samples of SLE patients and a pristane-induced lupus-like mouse model to examine the potential correlation of glatectin-3 with NETosis in SLE. Our results show that patients with SLE expressed higher levels of galectin-3 mRNA in the peripheral blood mononuclear cells than normal controls. Galectin-3 was detected in NETs of human neutrophils treated with phorbol 12-myristate 13-acetate (PMA) for inducing NETosis. Treatment with lactose, a galectin-3 inhibitor, reduced NETosis in a dose-dependent manner. In animal studies, we found that pristane-treated C57BL/6 mice exhibited immune complex deposition and had elevated galectin-3 expression in the hemorrhagic lung. Compared to wild-type mice, galectin-3 KO mice had lower levels of proteinuria, reduced pulmonary hemorrhage, decreased inflammatory cell infiltration, and enhanced survival time following pristane treatment. While NETosis and the NET marker citrullinated histone 3 were detectable in lipopolysaccharide (LPS)-treated neutrophils of wild-type mice, they were absent in their galactin-3 knockout counterparts. Furthermore, caspase activity was induced in neutrophils from galectin-3 knockout mice treated with LPS as compared with that from wild-type mice, suggesting that galectin-3 may play a pivotal role in shifting apoptosis to NETosis upon LPS stimulation. Taken together, our results suggest that galectin-3 may be involved in the pathogenesis of SLE through mediating NETosis.

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