Osteopontin is strongly expressed by alveolar macrophages in the lungs of acute respiratory distress syndrome.
Acute respiratory distress syndrome (ARDS) is characterized by an intense inflammatory response in the lung parenchyma. Recent studies suggest that excessive nitric oxide (NO) production mediated by inducible NO synthase (iNOS) in macrophages is partially involved in mediating acute lung injury in ARDS. On the other hand, osteopontin (OPN) is a cytokine which is capable of inhibiting NO production by suppressing iNOS mRNA expression in macrophages. In this study, we investigated the expression of OPN in the lungs of 10 patients with ARDS. In most patients, OPN is strongly expressed on alveolar macrophages. In addition, we produced a murine model for ARDS by intratracheal administration of lipopolysaccharide and investigated the expression of endogenous OPN and iNOS in the lungs of ARDS mice. Immunostaining demonstrated that in vivo OPN protein was coinduced with iNOS protein predominantly in the accumulating alveolar macrophages. OPN mRNA expression was also coinduced with iNOS mRNA, but was induced more slowly than iNOS mRNA in the lungs of ARDS mice. These results suggested that OPN, which may reduce NO production of macrophages by inhibiting iNOS expression, is significantly induced and expressed on alveolar macrophages in the lungs of ARDS. It is possible that OPN is partially involved in playing a protective role against excessive production of NO in ARDS.
Takahashi
Fumiyuki
F
Department of Respiratory Medicine, Juntendo University School of Medicine, Hongo, Bunkyo-Ku, Tokyo, Japan. fumiyuki@med.juntendo.ac.jp
Takahashi
Kazuhisa
K
Shimizu
Kazue
K
Cui
Ri
R
Tada
Norihiro
N
Takahashi
Hideki
H
Soma
Sanae
S
Yoshioka
Masakata
M
Fukuchi
Yoshinosuke
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D051379:Mice; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000378:metabolism; D053495:Osteopontin; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D012795:Sialoglycoproteins / Q000378:metabolism*; D014132:Trachea
D008070:Lipopolysaccharides; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin; D019001:Nitric Oxide Synthase