title: Ventilator-induced lung injury is associated with neutrophil infiltration, macrophage activation, and TGF-beta 1 mRNA upregulation in rat lungs.
abstract: Activated neutrophils contribute to the development of ventilator-induced lung injury (VILI) caused by high-pressure mechanical ventilation. However, exact cellular and molecular mechanisms have not been conclusively studied. Our investigation aimed to examine expression of adhesion molecules by both neutrophils and macrophages in lung lavage fluids of rats with VILI. Further, involvement of proinflammatory (tumor necrosis factor-alpha) and profibrogenetic (transforming growth factor-beta 1) mediators was analyzed at mRNA level in lung tissue. Wistar rats were ventilated by high pressure (45 cm H(2)O of peak inspiratory pressure, n = 23) or low pressure (7 cm H(2)O, n = 13) with 0 positive end-expiratory pressure. After 40 min of comparative ventilation, lung lavage was performed in 20 rats from the experimental group and 10 from the control for immunofluorescence analysis with anti-Mac-1 and anti-ICAM-1 monoclonal antibodies. The lung tissues from remaining rats were subjected to pathological and reverse transcription-polymerase chain reaction examinations. Although there was no significant change of PaO(2) in the low-pressure group, PaO(2) was decreased in the high-pressure group. The high-pressure group also had greater neutrophil infiltration into alveolar spaces, upregulation of CD54 and CD11b on alveolar macrophages, and more transforming growth factor-beta 1 mRNA in lung tissues. Tumor necrosis factor-alpha was not involved in the pathogenesis of the severe VILI observed. Histologic findings also demonstrated more infiltrating neutrophils, destructive change of the alveolar wall, and deposition of matrix in the high-pressure group. These results suggest that a series of proinflammatory reactions and profibrogenetic process may be involved in the course of VILI.
authors.affiliation: Surgical Intensive Care Unit, National Cardiovascular Center, Suita, Osaka, Japan. imanakah@hsp.ncvc.go.jp
authors.forename: H
authors.initials: H
authors.lastname: Imanaka
authors.forename: M
authors.initials: M
authors.lastname: Shimaoka
authors.forename: N
authors.initials: N
authors.lastname: Matsuura
authors.forename: M
authors.initials: M
authors.lastname: Nishimura
authors.forename: N
authors.initials: N
authors.lastname: Ohta
authors.forename: H
authors.initials: H
authors.lastname: Kiyono
mesh_terms: D000818:Animals; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008168:Lung / Q000378:metabolism* / Q000473:pathology*; D008262:Macrophage Activation; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017208:Rats, Wistar; D012121:Respiration, Artificial / Q000009:adverse effects*; D012128:Respiratory Distress Syndrome / Q000209:etiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation
chemical_list: D016177:Macrophage-1 Antigen; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1