Am. J. Respir. Cell Mol. Biol., Vol 10, No. 5, 05 1994, 481-486.
Blockade of leukocyte function-associated antigen (LFA-1) in a murine model of lung inflammation
M Denis and D Bisson
Pulmonary Research Unit, Faculty of Medicine, University of Sherbrooke, Canada.
We examined the contribution of the leukocyte function-associated antigen
(LFA-1) in a murine model of lung inflammation determined by exposure to
the thermophilic actinomycete Faeni rectivirgula. The exposure generated a
large influx of cells in the bronchoalveolar space and in the lung
parenchyma, as seen from enhanced numbers of cells recovered by
bronchoalveolar lavage (BAL) and histologic scoring of lung lesions.
Repeated intranasal exposure to F. rectivirgula also resulted in a
significant increase in lung hydroxyproline levels. Histologic analysis
showed that alveolar wall inflammation, interstitial swelling and
congestion, epithelial cell destruction, and granulomas with occasional
epithelioid cells were observed in the lungs of challenged mice. Mice
injected with rat antibodies against LFA-1 concomitantly with an antigen
challenge showed no reduction in the number of BAL inflammatory cells, but
lung fibrosis was significantly reduced by anti-LFA-1 treatment as assessed
by lung hydroxyproline levels; parenchymal inflammation and tissue damage
were also significantly reduced as seen from morphometric analysis.
Anti-LFA-1 treatment of mice with established hypersensitivity pneumonitis
was found to significantly reduce the levels of lung hydroxyproline and
tissue damage; the numbers of BAL cells remained unaffected. From these
results, we conclude that the fibrosis and tissue-damaging reactions in
hypersensitivity pneumonitis, but not the alveolitis, are partly dependent
on LFA-1-mediated cellular interactions.(ABSTRACT TRUNCATED AT 250 WORDS)
