Mj. Carr et al., DISTRIBUTION OF IMMUNOREACTIVE ENDOTHELIN IN THE LUNGS OF MICE DURINGRESPIRATORY VIRAL-INFECTION, The European respiratory journal, 11(1), 1998, pp. 79-85
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.