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Role of Surfactant Protein (SP)‐D in Vesicant‐induced Lung Toxicity
Author(s) -
Sunil Vasanthi,
Vayas Kinal,
Cervelli Jessica,
Goedken Michael,
Venosa Alessandro,
Malaviya Rama,
Laskin Jeffrey,
Laskin Debra
Publication year - 2015
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.29.1_supplement.774.3
Subject(s) - bronchoalveolar lavage , lung , inflammation , fibrosis , proinflammatory cytokine , pathology , pulmonary fibrosis , chemistry , collectin , hyperplasia , toxicity , edema , surfactant protein d , immunology , medicine , immune system , innate immune system
Nitrogen mustard (NM) is a vesicant that targets the lung and causes fibrosis. Evidence suggests that inflammatory macrophages (MP) contribute to the pathogenic response. SP‐D is a pulmonary collectin known to suppress MP activity. Herein, we analyzed the effects of loss of SP‐D on NM‐induced lung toxicity. Bronchoalveolar lavage (BAL) and lung tissue were collected from WT and SP‐D ‐/‐ mice 14 d after PBS or NM (0.08 mg/kg, i.t.). Treatment of WT mice with NM resulted in perivascular inflammation and increases in BAL cells and protein content, indicating alveolar epithelial injury. Loss of SP‐D resulted in a significant increase in the sensitivity of the mice to NM; thus, perivascular inflammation was more severe and there was evidence of foamy macrophages, perivascular edema, bronchiolar epithelial hypertrophy and hyperplasia, bronchiolar alveolar hyperplasia, bronchiectasis, fibrosis and emphysema. NM‐induced oxidative stress, assessed by MP hemeoxygenase‐1 expression, was also increased. Enlarged and highly vacuolated profibrotic Ym‐1 + and mannose receptor‐1 + MP were also present; in contrast, cyclooxygenase‐2 + proinflammatory MP were decreased. These data indicate that SP‐D plays an important role in protecting against NM‐induced pulmonary toxicity. Elucidating mechanisms regulating MP activity following NM exposure may be important in developing therapeutics to treat vesicant‐induced lung injury. Support: NIH AR055073 and ES005022.