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首页> 外文期刊>Journal of the American College of Surgeons >Polymerized hemoglobin induces heme oxygenase-1 protein expression and inhibits intercellular adhesion molecule-1 protein expression in human lung microvascular endothelial cells.
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Polymerized hemoglobin induces heme oxygenase-1 protein expression and inhibits intercellular adhesion molecule-1 protein expression in human lung microvascular endothelial cells.

机译:聚合血红蛋白在人肺微血管内皮细胞中诱导血红素加氧酶-1蛋白表达并抑制细胞间粘附分子-1蛋白表达。

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BACKGROUND: Our clinical trials using a polymerized hemoglobin solution (PolyHb) as a red cell substitute in severely injured patients suggested that this hemoglobin-based oxygen carrier has a systemic antiinflammatory effect. Heme oxygenase-1 (HO-1) has recently been shown to be cytoprotective, and is known to be induced by heme moieties. We investigated the effects of this hemoglobin-based oxygen carrier on HO-1 induction and proinflammatory activation of pulmonary endothelium. STUDY DESIGN: Human lung microvascular endothelial cells were grown to confluence and preincubated with either cell media (control) or with an equal volume mixture of polymerized hemoglobin/cell media (experimental). The cell cultures were subsequently stimulated with lipopolysaccharide. HO-1 expression was detected by protein immunoblot and further quantified by ELISA; intercellular adhesion molecule-1 protein expression was measured by flow cytometry. RESULTS: Polymerized hemoglobin induced synthesis of HO-1 protein in humanlung microvascular endothelial cells and, concurrently, inhibited lipopolysaccharide-induced intercellular adhesion molecule-1 protein cell surface expression. CONCLUSIONS: Polymerized hemoglobin attenuates lipopolysaccharide-stimulated expression of intercellular adhesion molecule-1 protein, which is associated with upregulation of the cytoprotective protein HO-1 in human pulmonary endothelial cells. This antiinflammatory effect offers a novel mechanism by which hemoglobin-based oxygen carrier solutions may be exploited therapeutically as resuscitative fluids.
机译:背景:我们在严重受伤的患者中使用聚合血红蛋白溶液(PolyHb)作为红细胞替代品的临床试验表明,这种基于血红蛋白的氧气载体具有全身性抗炎作用。血红素加氧酶-1(HO-1)最近被证明具有细胞保护作用,并且已知由血红素部分诱导。我们研究了这种基于血红蛋白的氧载体对HO-1诱导和肺内皮促炎激活的影响。研究设计:使人肺微血管内皮细胞生长至汇合,并与细胞培养基(对照)或等体积的聚合血红蛋白/细胞培养基混合物(实验)进行预孵育。随后用脂多糖刺激细胞培养物。通过蛋白免疫印迹检测HO-1的表达,并通过ELISA进一步定量;通过流式细胞术测量细胞间粘附分子1蛋白表达。结果:聚合血红蛋白诱导人肺微血管内皮细胞合成HO-1蛋白,同时抑制脂多糖诱导的细胞间粘附分子1蛋白细胞表面表达。结论:聚合血红蛋白减弱脂多糖刺激的细胞间粘附分子1蛋白的表达,这与人肺内皮细胞中细胞保护蛋白HO-1的上调有关。这种抗炎作用提供了一种新颖的机制,通过该机制,基于血红蛋白的氧气载体溶液可在治疗上用作复苏液。

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