Blockade of leukocyte function-associated antigen (LFA-1) in a murine model of lung inflammation.
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)
Denis
M
M
Pulmonary Research Unit, Faculty of Medicine, University of Sherbrooke, Canada.
Bisson
D
D
D000542:Alveolitis, Extrinsic Allergic / Q000150:complications / Q000276:immunology* / Q000473:pathology; D000818:Animals; D001203:Ascomycota / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004195:Disease Models, Animal; D005260:Female; D007167:Immunotherapy; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000517:prevention & control; D051381:Rats
D016169:Lymphocyte Function-Associated Antigen-1