肺泡巨噬细胞表达的诱导型一氧化氮合酶在高迁移率族蛋白B1诱导的急性肺损伤中的作用

Role of inducible nitric oxide synthase expressed by alveolar macrophages in high mobility group box 1--induced acute lung injury.

作者信息

Ren D, Sun R, Wang S

机构信息

Department of Pathophysiology, Institute of Basic Medical Sciences, Peking Union Medical College & Chinese Academy of Medical Sciences, 5 Dong Dan San Tiao, Beijing, 100005, People's Republic of China.

出版信息

Inflamm Res. 2006 May;55(5):207-15. doi: 10.1007/s00011-006-0072-2.

DOI:10.1007/s00011-006-0072-2

Abstract

OBJECTIVE AND DESIGN

The role of inducible nitric oxide synthase (iNOS) expressed by alveolar macrophages in acute lung injury induced by high mobility group box 1 (HMGB1) was explored.

TREATMENTS

Primary rat alveolar macrophages (PRAMs) were stimulated with HMGB1 to analyze iNOS expression. Alveolar macrophages and iNOS were inhibited by gadolinium chloride and 1400W in rats challenged by HMGB1 intratracheally.

METHODS

Western Blot was applied to assay iNOS expression in PRAMs. Indices for acute lung injury in rats were measured. Immunocytochemistry was used to localize iNOS in squarebronchoalveolar lavage (BAL) cells. The enzyme activities of iNOS and constitutive nitric oxide synthase (cNOS) for BAL cells were determined.

RESULTS

A time- and concentration-dependent response of iNOS expression in PRAMs to HMGB1 induction was observed. Intratracheal instillation of HMGB1 produced persistently exacerbated acute lung inflammation, induction of iNOS in alveolar macrophages and increased lung nitric oxide production in rats. Abrogation of iNOS or macrophages attenuated lung inflammation, nitric oxide in BAL fluid, and iNOS activity of BAL cells, but had no significant effect on cNOS activity of BAL cells in rats challenged by HMGB1.

CONCLUSIONS

Inducible nitric oxide synthase expressed by alveolar macrophages facilitates the development of HMGB1-induced acute lung injury.

摘要

目的与设计

探讨肺泡巨噬细胞表达的诱导型一氧化氮合酶（iNOS）在高迁移率族蛋白B1（HMGB1）诱导的急性肺损伤中的作用。

治疗方法

用HMGB1刺激原代大鼠肺泡巨噬细胞（PRAMs）以分析iNOS表达。在经气管内给予HMGB1攻击的大鼠中，用氯化钆和1400W抑制肺泡巨噬细胞和iNOS。

方法

采用蛋白质免疫印迹法检测PRAMs中iNOS的表达。测定大鼠急性肺损伤指标。用免疫细胞化学法对支气管肺泡灌洗（BAL）细胞中的iNOS进行定位。测定BAL细胞中iNOS和组成型一氧化氮合酶（cNOS）的酶活性。

结果

观察到PRAMs中iNOS表达对HMGB1诱导呈时间和浓度依赖性反应。气管内滴注HMGB1可使大鼠急性肺部炎症持续加剧，诱导肺泡巨噬细胞中iNOS表达，并增加肺一氧化氮生成。在经HMGB1攻击的大鼠中，抑制iNOS或巨噬细胞可减轻肺部炎症、BAL液中的一氧化氮含量以及BAL细胞的iNOS活性，但对BAL细胞的cNOS活性无显著影响。

结论

肺泡巨噬细胞表达的诱导型一氧化氮合酶促进了HMGB1诱导的急性肺损伤的发展。