title: Contributions of high mobility group box protein in experimental and clinical acute lung injury.
abstract: 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 (1) 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.
authors.affiliation: Department of Intensive Care and Anesthesiology, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueno
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Matsuda
authors.forename: Satoru
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Fumimasa
authors.initials: F
authors.lastname: Amaya
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kitamura
authors.forename: Masaki
authors.initials: M
authors.lastname: Tanaka
authors.forename: Atsuko
authors.initials: A
authors.lastname: Kobayashi
authors.forename: Ikuro
authors.initials: I
authors.lastname: Maruyama
authors.forename: Shingo
authors.initials: S
authors.lastname: Yamada
authors.forename: Naoki
authors.initials: N
authors.lastname: Hasegawa
authors.forename: Junko
authors.initials: J
authors.lastname: Soejima
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Koh
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Ishizaka
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D005260:Female; D024002:HMGB Proteins / Q000032:analysis* / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000378:metabolism* / Q000473:pathology
chemical_list: D024002:HMGB Proteins