title: A critical role for gelsolin in ventilator-induced lung injury.
abstract: Mechanical ventilation, an essential life-support modality of patients with acute lung injury (ALI) or the acute respiratory distress syndrome (ARDS), exerts its detrimental effects through largely unknown mechanisms. Gelsolin (GSN), an actin-binding protein and a substrate of caspase-3, was recently shown to play a major role in bleomycin- or lipopolysaccharide-induced lung injury. To dissect a possible role of GSN in the pathogenesis of ventilator-induced lung injury (VILI), genetically modified mice lacking GSN expression and wild-type controls underwent mechanical ventilation with high tidal volumes. GSN was found up-regulated in the airways upon VILI, and its genetic ablation led to almost complete disease protection as manifested by reduced edema formation, reduced lung injury, attenuated epithelial apoptosis, diminished cytokine expression, and impaired neutrophil infiltration. GSN fragmentation was shown to be an effector mechanism in VILI-induced apoptosis, while GSN expression was shown to be necessary for efficient neutrophil infiltration, which was found to be a prerequisite for VILI induction in this model. Therefore, intracellular GSN and GSN-mediated responses were shown to be an important player in the pathogenesis of VILI.
authors.affiliation: Marianthi Simou Lab, Evaggelismos Hospital, University of Athens Medical School, Athens, Greece.
authors.forename: Nikolaos A
authors.initials: NA
authors.lastname: Maniatis
authors.forename: Vaggelis
authors.initials: V
authors.lastname: Harokopos
authors.forename: Artemis
authors.initials: A
authors.lastname: Thanassopoulou
authors.forename: Nikos
authors.initials: N
authors.lastname: Oikonomou
authors.forename: Vassilis
authors.initials: V
authors.lastname: Mersinias
authors.forename: Walter
authors.initials: W
authors.lastname: Witke
authors.forename: Stylianos E
authors.initials: SE
authors.lastname: Orfanos
authors.forename: Apostolos
authors.initials: A
authors.lastname: Armaganidis
authors.forename: Charalambos
authors.initials: C
authors.lastname: Roussos
authors.forename: Anastasia
authors.initials: A
authors.lastname: Kotanidou
authors.forename: Vassilis
authors.initials: V
authors.lastname: Aidinis
mesh_terms: D000403:Airway Resistance; D000818:Animals; D017209:Apoptosis; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002199:Capillary Permeability; D016207:Cytokines / Q000378:metabolism; D018260:Gelsolin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006612:High-Frequency Ventilation / Q000009:adverse effects*; D008168:Lung / Q000473:pathology; D008170:Lung Compliance; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000473:pathology; D011654:Pulmonary Edema / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D013314:Stress, Mechanical; D055397:Ventilator-Induced Lung Injury / Q000209:etiology / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control
chemical_list: D016207:Cytokines; D018260:Gelsolin