Ventilator-induced lung injury is associated with neutrophil infiltration,macrophage activation, and TGF-beta 1 mRNA upregulation in rat lungs

Activated neutrophils contribute to the development of ventilator-induced l ung 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 bot h neutrophils and macrophages in lung lavage fluids of rats with VILI. Furt her, involvement of proinflammatory (tumor necrosis factor-alpha) and profi brogenetic (transforming growth factor-beta1) mediators was analyzed at mRN A level in lung tissue. Wistar rats were ventilated by high pressure (45 cm H2O of peak inspiratory pressure, n = 23) or low pressure (7 cm H2O, n = 1 3) with 0 positive end-expiratory pressure. After 40 min of comparative ven tilation, 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 we re subjected to pathological and reverse transcription-polymerase chain rea ction examinations. Although there was no significant change of PaO2 in the low-pressure group, PaO2 was decreased in the high-pressure group. The hig h-pressure group also had greater neutrophil infiltration into alveolar spa ces, upregulation of CD54 and CD11b on alveolar macrophages, and more trans forming growth factor-beta1 mRNA in lung tissues. Tumor necrosis factor-or was not involved in the pathogenesis of the severe VILI observed. Histologi c findings also demonstrated more infiltrating neutrophils, destructive cha nge of the alveolar wall, and deposition of matrix in the high-pressure gro up. These results suggest that a series of proinflammatory reactions and pr ofibrogenetic process may be involved in the course of VILI.