TY - JOUR
T1 - Contributions of high mobility group box protein in experimental and clinical acute lung injury
AU - Ueno, Hiroshi
AU - Matsuda, Tomoyuki
AU - Hashimoto, Satoru
AU - Amaya, Fumimasa
AU - Kitamura, Yoshihiro
AU - Tanaka, Masaki
AU - Kobayash, Atsuko
AU - Maruyama, Ikuro
AU - Yamada, Shingo
AU - Hasegawa, Naoki
AU - Soejima, Junko
AU - Koh, Hidefumi
AU - Ishizaka, Akitoshi
PY - 2004/12/15
Y1 - 2004/12/15
N2 - This study was performed to examine the putative role of high mobility group box (HMGB) protein in the pathogenesis of acute lung injury (ALI). Observations were made (7) in 21 patients who were septic with ALI and 15 patients with normal lung function and (2) in a mouse model 24 hours after intratracheal instillation of lipopolysaccharide (LPS). The concentrations of HMGB1 were increased in plasma and lung epithelial lining fluid of patients with ALI and mice instilled with LPS. LPS-induced ALI was mitigated by anti-HMGB1 antibody. Although this protein was not detected in the plasma of control humans or mice, the concentrations of HMGB1 in lung epithelial lining fluid or in bronchoalveolar lavage fluid were unexpectedly high. The nuclear expression of HMGB1 was apparent in epithelial cells surrounding terminal bronchioles in normal mice, whereas its nuclear and cytoplasmic expression was observed in alveolar macrophages in LPS-instilled mice. Lung instillation of HMGB2 did not cause as much inflammation as HMGB1. Extracellular HMGB1 may play a key role in the pathogenesis of clinical and experimental ALI. However, its expression in normal airways is noteworthy and suggests that it also plays a physiologic role in the lung.
AB - This study was performed to examine the putative role of high mobility group box (HMGB) protein in the pathogenesis of acute lung injury (ALI). Observations were made (7) in 21 patients who were septic with ALI and 15 patients with normal lung function and (2) in a mouse model 24 hours after intratracheal instillation of lipopolysaccharide (LPS). The concentrations of HMGB1 were increased in plasma and lung epithelial lining fluid of patients with ALI and mice instilled with LPS. LPS-induced ALI was mitigated by anti-HMGB1 antibody. Although this protein was not detected in the plasma of control humans or mice, the concentrations of HMGB1 in lung epithelial lining fluid or in bronchoalveolar lavage fluid were unexpectedly high. The nuclear expression of HMGB1 was apparent in epithelial cells surrounding terminal bronchioles in normal mice, whereas its nuclear and cytoplasmic expression was observed in alveolar macrophages in LPS-instilled mice. Lung instillation of HMGB2 did not cause as much inflammation as HMGB1. Extracellular HMGB1 may play a key role in the pathogenesis of clinical and experimental ALI. However, its expression in normal airways is noteworthy and suggests that it also plays a physiologic role in the lung.
KW - Acute respiratory distress syndrome
KW - Endotoxin
KW - High mobility group B-1 protein
KW - High mobility group B-2 protein
KW - Lipopolysaccharide
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U2 - 10.1164/rccm.200402-188OC
DO - 10.1164/rccm.200402-188OC
M3 - Article
C2 - 15374839
AN - SCOPUS:10644244296
VL - 170
SP - 1310
EP - 1316
JO - American Review of Respiratory Disease
JF - American Review of Respiratory Disease
SN - 1073-449X
IS - 12
ER -