ICAM-1 mediates lung leukocyte recruitment but not pulmonary fibrosis in a murine model of bleomycin-induced lung injury.
Bleomycin-induced lung injury has been extensively used as a model of interstitial pneumonia and pulmonary fibrosis. Intercellular adhesion molecule (ICAM)-1 is a ligand for lymphocyte function-associated antigen (LFA)-1alpha and has been shown to be required for leukocyte migration into inflamed areas. The purpose of this report was to investigate the role of the ICAM-1/LFA-1alpha pathway in a murine model of bleomycin-induced lung injury. Animals received 75 mg x kg(-1) bleomycin (BLM) i.v. followed by treatment with phosphate-buffered saline (BLM group), anti-ICAM-1 and LFA-1alpha monoclonal antibodies (mAb) (BLM+mAb group). Inflammatory cell counts of bronchoalveolar lavage (BAL) fluid, hydroxyproline content and histological findings were compared between these groups. In the BLM group, significant increases in total cell count, macrophage count and neutrophil count of BAL fluid were observed on days 7 and 14. In the BLM+mAb group, bleomycin-induced accumulation of neutrophils was significantly reduced on days 7 and 14 (p<0.01). However, the administration of mAb to ICAM-1 and LFA-1alpha did not decrease the lung hydroxyproline content or the histopathological fibrosis grading score, indicating that the antagonism of ICAM-I and LFA-1alpha did not attenuate bleomycin-induced pulmonary fibrosis. This study suggests that the intercellular adhesion molecule-1/lymphocyte function-associated antigen-1alpha pathway mediates the accumulation of inflammatory cells in the injured lung caused by bleomycin; however, other mechanisms are important for the subsequent development of pulmonary fibrosis.
Matsuse
T
T
Dept of Geriatrics, Faculty of Medicine, University of Tokyo, Japan.
Teramoto
S
S
Katayama
H
H
Sudo
E
E
Ekimoto
H
H
Mitsuhashi
H
H
Uejima
Y
Y
Fukuchi
Y
Y
Ouchi
Y
Y
D000818:Animals; D001761:Bleomycin / Q000008:administration & dosage; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002465:Cell Movement; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D007958:Leukocyte Count; D007962:Leukocytes / Q000276:immunology*; D008168:Lung / Q000166:cytology*; D008297:Male; D051379:Mice; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology
D001761:Bleomycin; D018799:Intercellular Adhesion Molecule-1