DISTRIBUTION OF IMMUNOREACTIVE ENDOTHELIN IN THE LUNGS OF MICE DURINGRESPIRATORY VIRAL-INFECTION

Respiratory tract viral infections are associated with the generation of a wide array of pro-inflammatory cytokines, some of which enhance t he release of the potent airway smooth muscle spasmogen, endothelin, f rom respiratory epithelial cells in tissue culture, The aim of this st udy was to determine whether the content and distribution of immunorea ctive endothelin in the intact murine lung is increased during the cou rse of a respiratory tract viral infection. Mice were inoculated intra nasally with Influenza A/PR-8/34 virus or sterile vehicle and at vario us days postinoculation were sacrificed, and their lungs processed for either fluorescence immunohistochemistry with rabbit anti-endothelin sera or measurement of immunoreactive endothelin with an enzyme-linked immunosorbent assay (ELISA). At 2 and 4 days postinoculation, the con tent of immunoreactive endothelin in lung extracts of virus-infected m ice was approximately twice that present in lung extracts from control mice (n=3-4, p<0.05), Consistent with this, an increased intensity an d broader distribution of fluorescent immunohistochemical staining for endothelin was observed in the airway epithelium of the trachea and i ntrapulmonary airways of virus-infected mice, This study has clearly d emonstrated that respiratory tract viral infection is associated with an increased content and broader distribution of immunoreactive endoth elin within the lungs of mice, Whether the elevated content of endothe lin contributes to the symptoms of virus-induced hyperresponsiveness o r to virus-induced exacerbations of asthma remains to be established.