Lack of both α2-antiplasmin and plasminogen activator inhibitor type-1 induces high IgE production
Lack of both α2-antiplasmin and plasminogen activator inhibitor type-1 induces high IgE production
复制标题
缺乏 α2-抗纤溶酶和 1 型纤溶酶原激活剂抑制剂会诱导高 IgE 产生
DOI：
10.1016/j.lfs.2013.05.023
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发表时间：
2013
期刊：
影响因子：
6.1
通讯作者：
and Matsuo O
中科院分区：
文献类型：
--
作者：
Okada K;Ueshima S;Kawao N;Yano M;Tamura Y;Tanaka M;Sakamoto A;Hatano M;Arima M;Miyata S;Nagai N;Tokuhisa T;and Matsuo O
目的研究α2-抗纤溶酶(α2-AP)和纤溶酶原激活物抑制物-1(PAI-1)基因缺失小鼠的病理生理变化，阐明纤溶抑制物在免疫应答中的作用。比较α-2-AP/PAI1-Double KO小鼠和野生型(WT)小鼠的肺、肝、肾、脾组织。在此基础上，将α2-AP/PAI-1-Double KO小鼠的骨髓细胞移植到10GyX射线照射的WT小鼠体内，观察移植效果。在血管周围聚集的淋巴细胞中检测到产生IgE的浆细胞。在PAI2-AP/α-1-Double KO小鼠中，肺、肝、肾可见血管周围淋巴细胞浸润，肺内可见支气管周围淋巴细胞浸润。将α2-AP/PAI-1-Double KO小鼠的骨髓细胞移植到10GyX射线照射的WT小鼠体内，其表型与α2-AP/PAI-1-Double KO小鼠相似。此外，提示PAI2-AP和α-1均参与外周组织中淋巴细胞的募集。
AimsWe investigated the pathophysiological changes in mice lacking α2-antiplasmin (α2-AP) and plasminogen activator inhibitor type-1 (PAI-1) genes, and elucidated the involvement of these inhibitors for fibrinolysis in immune response.Main methodsThe pathophysiological changes induced by a lack of both α2-AP and PAI-1 were investigated using double knockout (KO) mice. The lung, liver, kidney and spleen tissues from α2-AP/PAI-1-double KO mice were compared with those from wild-type (WT) mice. Furthermore, the bone marrow cells from α2-AP/PAI-1-double KO mice were transplanted into 10-Gy X ray irradiated WT mice, and then the effects of the transplantation were studied.Key findingsPlasma IgE levels in the α2-AP/PAI-1-double KO mice increased with age and exceeded 1000 ng/mL after 6 months of age. The plasma cells that produced IgE were detected in perivascular assembled lymphocytes. In the α2-AP/PAI-1-double KO mice, perivascular lymphocyte infiltration was observed in the lung, liver, and kidneys and peribronchial lymphocyte infiltration was present in the lung. When the bone marrow cells from α2-AP/PAI-1-double KO mice were transplanted into 10-Gy X ray irradiated WT mice, the phenotypes of the recipients were similar to those of α2-AP/PAI-1-double KO mice.SignificanceThe simultaneous expression of both the α2-AP and PAI-1 genes contributes to the maintenance of immunological functions that are related to IgE. Moreover, it is suggested that both α2-AP and PAI-1 are involved in the recruitment of lymphocytes in the peripheral tissues.