K. Kumagai et al., Inhibition of matrix metalloproteinases prevents allergen-induced airway inflammation in a murine model of asthma, J IMMUNOL, 162(7), 1999, pp. 4212-4219
Although matrix metalloproteinases (MMPs) have been reported to play crucia
l roles in the migration of inflammatory cells through basement membrane co
mponents in vitro, the role of MMPs in the in vivo accumulation of the cell
s to the site of inflammation in bronchial asthma is still obscure, In this
study, we investigated the role of MMPs in the pathogenesis of bronchial a
sthma, using a murine model of allergic asthma, In this model, we observed
the increase of the release of MMP-2 and MMP-9 in bronchoalveolar lavage fl
uids after ag inhalation in the mice sensitized with OVA, which was accompa
nied by the infiltration of lymphocytes and eosinophils, Administration of
tissue inhibitor of metalloproteinase-2 to airways inhibited the Bg-induced
infiltration of lymphocytes and eosinophils to airway wall and lumen, redu
ced Ag-induced airway hyperresponsiveness, and increased the numbers of eos
inophils and lymphocytes in peripheral blood, The inhibition of cellular in
filtration to airway lumen was observed also with tissue inhibitor of metal
loproteinase-1 and a synthetic matrix metalloproteinase inhibitor. These da
ta suggest that MMPs, especially MMP-2 and MMP-9, are crucial for the infil
tration of inflammatory cells and the induction of airway hyperresponsivene
ss, which are pathophysiologic features of bronchial asthma, and further ra
ise the possibility of the inhibition of MMPs as a therapeutic strategy of
bronchial asthma.