Surfactant protein D protects against acute hyperoxic lung injury

被引:42
作者
Jain, Deepika [1 ]
Atochina-Vasserman, Elena N. [1 ]
Tomer, Yaniv [1 ]
Kadire, Helchem [1 ]
Beers, Michael F. [1 ]
机构
[1] Univ Penn, Sch Med, Div Pulm & Crit Care, Surfactant Biol Labs, Philadelphia, PA 19104 USA
基金
美国国家卫生研究院;
关键词
innate immunity; inflammation; collectin; antioxidants; oxidative stress;
D O I
10.1164/rccm.200804-582OC
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Rationale: Surfactant protein D (SP-D) is a member of the collectin family of soluble, innate, host defense molecules with demonstrated immunomodulatory properties in vitro. Constitutive absence of SP-D in mice is associated with lung inflammation, alteration in surfactant lipid homeostasis, and increased oxidative-nitrative stress. Objectives: To test the hypothesis that SP-D would protect against acute lung injury from hyperoxia in vivo. Methods: Transgenic mice overexpressing rat SP-D constitutively (SP-D OE) or conditionally via regulation with doxycycline (SP-D Dox-on) were subjected to continuous hyperoxic challenge for up to 14 days. Measurements and Main Results: Compared with littermate control mice (wild-type [WT]), SP-D OE mice exposed to 80% O-2 demonstrated substantially increased survival accompanied by significant reductions in wet to dry lung ratios and bronchoalveolar lavage (BAL) protein. Although SP-D OE and WT mice exhibited a twofold increase in total BAL cells and neutrophilia in response to hyperoxia, the SP-D OE group had lower levels of BAL proinflammatory cytokines and chemokines, including IL-6, tumor necrosis factor-alpha, and monocyte chemotactic protein-1; increased mRNA levels of the transcription factor NF-E2 related factor-2 (NRF-2) and phase 2 antioxidants hemoxygenase-1 (HO-1), glutathione peroxidase-2 (GPx-2) and NAD(P)H quinone oxidoreductase-1 (Nqo-1); and decreases in lung tissue thiobarbituric acid-reactive substances. As proof of principle, the protective role of SP-D on hyperoxic injury was confirmed as SP-D Dox-on mice exposed to 85% O-2 demonstrated increased mortality upon withdrawal of doxycycline. Conclusions: Local expression of SP-D protects against hyperoxic lung injury through modulation of proinflammatory cytokines and antioxidant enzymatic scavenger systems.
引用
收藏
页码:805 / 813
页数:9
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