Class A scavenger receptor (CD204) attenuates hyperoxia-induced lung injury by reducing oxidative stress
Class A scavenger receptor (CD204) attenuates hyperoxia-induced lung injury by reducing oxidative stress
复制标题
DOI：
10.1002/path.2150
复制
发表时间：
2007-05-01
影响因子：
7.3
通讯作者：
Takeya, M.
中科院分区：
文献类型：
--
作者：
Kobayashi, H.;Sakashita, N.;Takeya, M.
为了阐明巨噬细胞A类清道夫受体（SR-A，CD 204）在氧化性肺损伤中的作用，我们检查了SR-A缺陷（SR-A（-/-））和野生型（SR-A（-/-））小鼠对高氧治疗的肺组织反应。SR-A（-/-）小鼠的支气管肺泡灌洗液（BALF）蛋白水平和肺水肿（湿/干重比）高于SR-A（+/+）小鼠。SR-A（-/-）小鼠的累积存活率显著降低。但两组BALF中巨噬细胞和中性粒细胞计数无差异。实时荧光定量逆转录-聚合酶链反应（RTPCR）显示，高氧损伤时诱导型一氧化氮合酶（iNOS）mRNA水平升高，且这种升高在SR-A（-/-）小鼠中更为明显。在体内外高氧条件下，SR-A（-/-）组肺泡巨噬细胞iNOS表达水平均高于SR-A（+/+）组。使用抗硝基酪氨酸抗体的免疫组织化学显示，在两组中损伤的肺中存在独特的氧化应激，但在SR-A（-/-）小鼠中更为显著。高氧治疗后，SR-A（-/-）小鼠肺肿瘤坏死因子-α（TNF-α）mRNA水平升高速度快于SR-A（+/+）小鼠。总之，这些结果表明，SR-A表达减弱高氧诱导的肺损伤，减少巨噬细胞活化。版权所有（c）2007大不列颠和爱尔兰病理学会。由John Wiley & Sons有限公司出版
To clarify the role of macrophage class A scavenger receptors (SR-A, CD204) in oxidative lung injury, we examined lung tissue of SR-A deficient (SR-A(-/-)) and wild-type (SR-A(-/-)) mice in response to hyperoxic treatment. Protein levels of bronchoalveolar lavage fluid (BALF) and pulmonary oedema (wet: dry weight ratios) were higher in SR-A(-/-) mice than those in SR-A(+/+) mice. Cumulative survival was significantly decreased in SR-A(-/-) mice. However, there were no differences in BALF macrophage and neutrophil count between the two groups. Real-time reverse transcriptase-polymerase chain reaction (RTPCR) revealed that messenger RNA (mRNA) levels of the inducible nitric oxide synthase (iNOS) were increased during hyperoxic injury, and this increase was more prominent in SR-A(-/-) mice. Expression levels of iNOS in alveolar macrophages after hyperoxia in vivo and in vitro were higher in SR-A(-/-) macrophages compared with SR-A(+/+) macrophages. Immunohistochemistry using anti-nitrotyrosine antibodies revealed distinctive oxidative stress in the injured lung in both groups, but it was more remarkable in the SR-A(-/-) mice. After hyperoxic treatment, pulmonary mRNA levels of tumour necrosis factor-alpha(TNF-alpha) were elevated more rapidly in SR-A(-/-) mice than in SR-A(+/+) mice. Together these results suggest that SR-A expression attenuates hyperoxia-induced lung injury by reducing macrophage activation. Copyright (c) 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.