Heme is a potent inducer of inflammation in mice and is counteracted by heme oxygenase
Heme is a potent inducer of inflammation in mice and is counteracted by heme oxygenase
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DOI：
10.1182/blood.v98.6.1802
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发表时间：
2001-09-15
期刊：
影响因子：
20.3
通讯作者：
Figdor, CG
中科院分区：
文献类型：
--
作者：
Wagener, FADTG;Eggert, A;Figdor, CG
各种病理条件，如出血，溶血和细胞损伤，其特征在于释放大量血红素。最近，它被证明，血红素氧合酶（HO），血红素降解酶，和血红素能够调节粘附分子的表达在体外。在本研究中，血红素和HO对小鼠炎症的影响进行了分析，通过监测放射性标记的脂质体和白细胞的生物分布结合免疫组织化学。由于局部血管通透性增强，小脂质体通过扩散聚集在炎症组织中，而白细胞通过与内皮细胞的特异性粘附相互作用和趋化性主动迁移到炎症区域。暴露于血红素导致胰腺中脂质体积累的急剧增加，但肠、肝和脾也表现出显著增加的血管通透性。同样，静脉注射血红素引起放射性标记的白细胞流入这些器官的增加。免疫组织化学分析显示，血红素处理的动物的肝脏和胰腺中的粘附分子ICAM-1，P-选择素和纤连蛋白的差异上调。血红素诱导的粘附特性伴随着大量的粒细胞流入这些炎症组织，这表明炎症过程的发病机制的重要贡献。此外，HO活性的抑制加剧血红素诱导的粒细胞浸润。在这里，它是第一次证明，血红素诱导血管通透性增加，粘附分子的表达，和白细胞招募在体内，而HO拮抗血红素诱导的炎症可能通过下调粘附分子。(C)2001年，美国血液学会。
Various pathologic conditions, such as hemorrhage, hemolysis and cell injury, are characterized by the release of large amounts of heme. Recently, it was demonstrated that heme oxygenase (HO), the heme-degrading enzyme, and heme are able to modulate adhesion molecule expression in vitro. In the present study, the effects of heme and HO on inflammation in mice were analyzed by monitoring the biodistribution of radiolabeled liposomes and leukocytes in conjunction with immunohistochemistry. Small liposomes accumulate in inflamed tissues by diffusion because of locally enhanced vascular permeability, whereas leukocytes actively mi-grate into inflammatory areas through specific adhesive interactions with the endothelium and chemotaxis. Exposure to heme resulted in a dramatic increase in liposome accumulation in the pancreas, but also intestines, liver, and spleen exhibited significantly increased vascular permeability. Similarly, intravenously administered heme caused an enhanced influx of radiolabeled leukocytes into these organs. Immunohistochemical analysis showed differential up-regulation of the adhesion molecules ICAM-1, P-selectin, and fibronectin in liver and pancreas in heme-treated animals. Heme-induced adhesive properties were accompanied by a massive influx of granulocytes into these inflamed tissues, suggesting an important contribution to the pathogenesis of inflammatory processes. Moreover, inhibition of HO activity exacerbated heme-induced granulocyte infiltration. Here it is demonstrated for the first time that heme induces increased vascular permeability, adhesion molecule expression, and leukocyte recruitment in vivo, whereas HO antagonizes heme-induced inflammation possibly through the down-modulation of adhesion molecules. (C) 2001 by The American Society of Hematology.