Guanylate-binding protein-1 expression is selectively induced by inflammatory cytokines and is an activation marker of endothelial cells during inflammatory diseases
Guanylate-binding protein-1 expression is selectively induced by inflammatory cytokines and is an activation marker of endothelial cells during inflammatory diseases
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DOI：
10.1016/s0002-9440(10)64452-5
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发表时间：
2002-11-01
影响因子：
6
通讯作者：
Stürzl, M
中科院分区：
文献类型：
--
作者：
Lubeseder-Martellato, C;Guenzi, E;Stürzl, M
在血管生成和炎症过程中，内皮细胞获得不同的激活表型，其识别有助于理解体内血管生成和炎症相互作用的复杂网络。为此，我们研究了炎性细胞因子(ICs)高度诱导的人类鸟苷结合蛋白(GBP)-1的表达，因此，它可能是IC激活的细胞的特征。利用一种新的大鼠抗GBP-1的单抗，我们证明了GBP-1是一种细胞质蛋白，其在内皮细胞中的表达可被干扰素-γ、白介素1α、白介素1β或肿瘤坏死因子选择性地诱导，但不受其他细胞因子、趋化因子或生长因子的诱导。此外，我们发现GBP-1的表达与血管内皮细胞高度相关，在广泛的人体组织中，GBP-1和内皮细胞相关标记CD31的同时检测证实了这一点。值得注意的是，GBP-1在皮肤中检测不到，但在具有高度炎症成分的皮肤病的血管中高度诱导，包括牛皮癣、药物不良反应和卡波西氏肉瘤。这些结果表明，GBP-1是一种新的细胞激活标记，它表征内皮细胞IC激活的表型。
During angiogenesis and inflammatory processes, endothelial cells acquire different activation phenotypes, whose identification may help in understanding the complex network of angiogenic and inflammatory interactions in vivo. To this goal we investigated the expression of the human guanylate-binding protein (GBP)-1 that is highly induced by inflammatory cytokines, (ICs) and, therefore, may characterize IC-activated cells. Using a new rat monoclonal antibody raised against GBP-1, we show that GBP-1 is a cytoplasmic protein and that its expression in endothelial cells is selectively induced by interferon-gamma, interleukin-1alpha, interleukin-1beta, or tumor necrosis factor-a, but not by other cytokines, chemokines, or growth factors. Moreover, we found that GBP-1 expression is highly associated with vascular endothelial cells as confirmed by the simultaneous detection of GBP-1 and the endothelial cell-associated marker CD31 in a broad range of human tissues. Notably, GBP-1 expression was undetectable in the skin, but it was highly induced in vessels of skin diseases with a high-inflammatory component including psoriasis, adverse drug reactions, and Kaposi's sarcoma. These results indicate that GBP-1 is a novel cellular activation marker that characterizes the IC-activated phenotype of endothelial cells.