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Am J Respir Crit Care Med. 2008 Oct 15;178(8):805-13. doi: 10.1164/rccm.200804-582OC. Epub 2008 Jul 17.

Surfactant protein D protects against acute hyperoxic lung injury.

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  • 1Pulmonary and Critical Care Division, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-4539, USA.

Abstract

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.

PMID:
18635887
[PubMed - indexed for MEDLINE]
PMCID:
PMC2566792
Free PMC Article
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