Surfactant protein D protects against acute hyperoxic lung injury.
BACKGROUND
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.


OBJECTIVE
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.


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.
Jain
Deepika
D
Pulmonary and Critical Care Division, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-4539, USA.
Atochina-Vasserman
Elena N
EN
Tomer
Yaniv
Y
Kadire
Helchem
H
Beers
Michael F
MF
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D015870:Gene Expression; D018496:Hyperoxia / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D015151:Immunoblotting; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress; D037663:Pulmonary Surfactant-Associated Protein D / Q000096:biosynthesis / Q000235:genetics*; D012313:RNA / Q000235:genetics*; D051381:Rats; D012128:Respiratory Distress Syndrome / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016207:Cytokines; D037663:Pulmonary Surfactant-Associated Protein D; D012313:RNA