Inflammatory mechanisms of pulmonary injury induced by mustards

Abstract

Exposure of humans and animals to vesicants, including sulfur mustard (SM) and nitrogen mustard (NM), causes severe and debilitating damage to the respiratory tract. Both acute and long term pathological consequences are observed in the lung following a single exposure to these vesicants. Evidence from our laboratories and others suggest that macrophages and the inflammatory mediators they release play an important role in mustard-induced lung injury. In this paper, the pathogenic effects of SM and NM on the lung are reviewed, along with the potential role of inflammatory macrophages and mediators they release in mustard-induced pulmonary toxicity.

Keywords: Lung injury; Pulmonary toxicity; TNFα; Vesicant; iNOS.

Fig. 1. Effects of NM on histopathology of the lung

Lung sections, prepared 3 d after exposure of rats to NM or control (PBS) were stained with H & E. NM-induced acute structural changes include multifocal inflammatory lesions (*), characterized by accumulation of inflammatory cells in alveolar spaces (arrow), thickened bronchial epithelium (arrow head), perivascular edema (e), hyperproliferation and hypertrophy of goblet cells (g) and fibrin deposits (f). Original magnification, 4× (top panels), 200× (bottom panels). Representative section from 3 – 7 rats/treatment group are shown.

Fig. 2. Effects of NM exposure on expression of proinflammatory and profibrotic proteins

Lung sections, prepared 3 d and 28 d after exposure of rats to NM or control (PBS), were stained with antibody to COX-2, iNOS, Ym-1 or Gal-3. Binding was visualized using a Vectastain kit. Original magnification, 600×. Representative section from 3 – 7 rats/treatment group are shown. Control, 3 d post PBS exposure.