Tumor necrosis factor-alpha up-regulation in spontaneously proliferating cells derived from bovine leukemia virus-infected cattle
Tumor necrosis factor-alpha up-regulation in spontaneously proliferating cells derived from bovine leukemia virus-infected cattle
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DOI：
10.1007/s00705-005-0622-x
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发表时间：
2006-02-01
影响因子：
2.7
通讯作者：
Onuma, M
中科院分区：
文献类型：
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作者：
Konnai, S;Usui, T;Onuma, M
肿瘤坏死因子-α（TNF-α）是牛白血病病毒（BLV）引起白血病的细胞因子之一。为了确定在疾病晚期观察到的自发细胞增殖，如持续性淋巴细胞增多和淋巴肉瘤，是否与TNF-α的表达水平相关，我们分析了来自BLV感染牛的自发增殖PBMC中TNF-α的mRNA表达水平。BLV感染牛的自发增殖PBMC中TNF-α的平均mRNA表达水平高于正常牛的非自发增殖PBMC。通过流式细胞术分析确定PBMC中的TNF-α蛋白水平，并且注意到在自发增殖细胞中表达膜结合TNF-α的细胞大多数是CD 5或sIgM（+）-细胞。此外，为了确定这种自发增殖是否可以被抗牛TNF-α MAb阻断，在MAb存在下培养来自BLV感染的牛的自发增殖的PBMC。在72 h培养开始时添加该MAb以剂量依赖性方式明显抑制细胞的自发增殖，表明TNF-α直接参与疾病晚期PBMC的自发增殖。这些数据表明，TNF-α的异常表达可能有助于发展持续性B细胞淋巴细胞增多症或B细胞淋巴肉瘤的动物中牛白血病的进展。
We previously reported that tumor necrosis factor alpha (TNF-alpha) was one of the cytokines that contributed to the leukemogenesis caused by bovine leukemia virus (BLV). To determine if the spontaneous cell proliferation observed in the late disease stages, such as persistent lymphocytosis and lymphosarcoma, correlated with the expression level of TNF-alpha, we analyzed the mRNA expression levels for TNF-alpha in spontaneously proliferating PBMCs derived from BLV-infected cattle. The mean mRNA expression level for TNF-alpha was higher in the spontaneously proliferating PBMCs derived from BLV-infected cattle than in non-spontaneously proliferating PBMCs from normal cattle. The TNF-alpha protein level in the PBMCs was determined by flow cytometric analysis, and it was noted that most of the cells expressing membrane-bound TNF-alpha in the spontaneously proliferating cells were CD5 or sIgM(+) -cells. Additionally, in order to determine if this spontaneous proliferation can be blocked by anti-bovine TNF-alpha MAb, the spontaneously proliferating PBMCs from a BLV-infected cattle were cultured in the presence of the MAb. The addition of this MAb at the beginning of the 72 h-cultivation clearly inhibited spontaneous proliferation of cells in a dose-dependent manner, indicating the direct involvement of TNF-alpha in the spontaneous proliferation of PBMCs during the late disease stage. These data suggest that an aberrant expression of TNF-alpha might contribute to the progression of bovine leukosis in animals which develop persistent lymphocytosis of B-cells or B-cell lymphosarcoma.