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Surfactant Protein D Protects Against Hyperoxia‐Induced Acute Lung Injury In A Murine Model
Author(s) -
Jain Deepika,
AtochinaVasserman Ele.,
Kadire Helchem,
Tomer Yaniv,
Inch Adam,
Beers Michael F.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1441-c
Subject(s) - hyperoxia , lung , inflammation , surfactant protein a , in vivo , chemokine , pulmonary edema , chemistry , endocrinology , pulmonary surfactant , medicine , andrology , microbiology and biotechnology , immunology , biology , biochemistry
Surfactant Protein D (SP‐D), a 43kDa member of the collectin family, plays a key role in modulating inflammation and innate immunity in the lung. Targeted disruption of SP‐D gene in mice induces pulmonary inflammation, alteration in surfactant lipid homeostasis and increased oxidative‐nitrative stress. Lung specific overexpression of a rat SP‐D transgene in vivo has generated mice with an abundance of rat SP‐D in BAL (SP‐D OE), but no effect on lung morphology, phospholipid content or other surfactant protein mRNAs as compared to the wild type mice (WT). Hypothesis SP‐D protects against acute lung injury from hyperoxia in vivo.Results SP‐D OE and littermate WT mice were continuously exposed to 80% or 21% oxygen. 80% of SP‐D OE mice survived as compared to 5% WT after 7 days of hyperoxia. When assessed after 5 days of exposure, SP‐D OE mice showed significantly lower weight loss (10% vs. 24% in WT) and less pulmonary edema estimated both as a reduction in wet to dry lung ratios (6% vs. 24% in WT) and as decreased protein leak in the alveoli. Whereas hyperoxic WT mice exhibited a 2‐fold increase in total BAL cells with a significant influx of neutrophils, total BAL cells from SP‐D OE mice did not increase despite similar neutrophil infiltration. From a multiplex assay of BAL for nine cytokines (SearchLight® Technology), we found that SP‐D OE mice had significantly lower levels of pro‐inflammatory cytokines and chemokines such as IL‐6, GM‐CSF and JE/MCP‐1 in BAL fluid as compared to WT. Conclusions Overexpression of SP‐D in mice protects against hyperoxic lung injury by regulating pro‐inflammatory cytokines and restricting cell infiltration and alveolar protein leak. Funded by NIH HL 64520 and P50‐000428 (to MFB)