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INTRODUCTION

Pulmonary ischemia-reperfusion (IR) injury (IRI) plays a significant role in various lung disorders and is a key factor in the development of primary graft dysfunction following lung transplantation. Hemopexin (Hx) is the major serum scavenger protein for heme, which is a prooxidant and pro-inflammatory compound. In the current study, we hypothesized that Hx could confer beneficial effects in sterile inflammation induced by IR-mediated lung injury.

METHODS

To examine this hypothesis, we administered Hx in an experimental mouse model of unilateral lung IRI.

RESULTS

Our results demonstrate that treatment with Hx alleviated histopathological signs of inflammation in ischemic lungs, as evidenced by a reduction in the number of infiltrating neutrophils and decreased levels of perivascular edema. In addition, thrombotic vaso-occlusion in pulmonary blood vessels of IRI lungs was reduced by Hx. Immunohistochemical analysis revealed that Hx inhibited the up-regulation of heme oxygenase-1, an enzyme highly induced by heme, in ischemic lungs. Finally, Hx administration caused a decrease in the levels of circulating B- and CD8+ T-lymphocytes in the peripheral blood of mice with pulmonary IRI.

CONCLUSION

These findings suggest that the serum heme scavenger protein Hx holds therapeutic promise in alleviating lung IRI-mediated sterile inflammation. Thus, Hx may represent a preemptive therapeutic approach in IR-related lung disorders such as primary graft dysfunction in lung transplantation.

INTRODUCTION

METHODS

To examine this hypothesis, we administered Hx in an experimental mouse model of unilateral lung IRI.

RESULTS

CONCLUSION

简介

肺缺血再灌注（IR）损伤（IRI）在各种肺部疾病中起着重要作用，是肺移植后原发性移植物功能障碍发展的关键因素。血红素结合蛋白（Hx）是血红素的主要血清清除蛋白，血红素是一种促氧化剂和促炎化合物。在本研究中，我们假设 Hx 可以在由 IR 介导的肺损伤引起的无菌性炎症中发挥有益作用。

方法

为了检验这一假设，我们在单侧肺 IRI 的实验性小鼠模型中给予 Hx。

结果

我们的结果表明，Hx 治疗减轻了缺血肺的炎症组织病理学迹象，表现为浸润中性粒细胞数量减少和血管周围水肿程度降低。此外，Hx 减少了 IRI 肺中肺血管的血栓性血管阻塞。免疫组织化学分析显示，Hx 抑制了缺血肺中血红素高度诱导的血红素加氧酶-1的上调。最后，Hx 给药导致肺 IRI 小鼠外周血中循环 B 和 CD8+T 淋巴细胞水平降低。