Official websites use. Share sensitive information only on official, secure websites. Fax: E-mail: sunilva pharmacy. Nitrogen mustard NM is a vesicant known to cause acute pulmonary injury which progresses to fibrosis.
Macrophages contribute to both of these pathologies. Surfactant protein SP -D is a pulmonary collectin that suppresses lung macrophage activity. Herein, we analyzed the effects of loss of SP-D on NM-induced macrophage activation and lung toxicity. Bronchoalveolar lavage BAL fluid and tissue were collected 14 days later.
Flow cytometric analysis of BAL cells from NM treated WT mice revealed the presence of proinflammatory and anti-inflammatory macrophages. Loss of SP-D also exacerbated NM-induced oxidative stress and alveolar epithelial injury, as reflected by increases in heme oxygenase-1 expression, and BAL cell and protein content. This was correlated with alterations in pulmonary mechanics. These data demonstrate that activated lung macrophages play a role in NM-induced lung injury and oxidative stress.
Elucidating mechanisms regulating macrophage activity may be important in developing therapeutics to treat mustard-induced lung injury. Keywords: SP-D, nitrogen mustard, vesicants, macrophages, inflammation, lung injury, oxidative stress. Nitrogen mustard NM is a cytotoxic vesicant known to target the lung. Both acute and long-term effects have been described following NM exposure, including inflammation and disruption of the alveolar epithelial barrier, hemorrhage, edema, intra-alveolar septal thickening, bronchiolitis, and pulmonary fibrosis Sunil et al.
Toxicity results from alkylation and cross-linking of a variety of cellular components including nucleic acids, proteins, and lipids, leading to impairment of cellular functioning and cell death; this is associated with oxidative and nitrosative stress Korkmaz et al. Inflammatory macrophages accumulating in the lung in response to NM-induced injury have been implicated in its pathogenic effects by promoting oxidative and nitrosative stress and releasing proinflammatory, cytotoxic, and profibrotic mediators Malaviya et al.
