These data show for the first time that otherwise noninjurious mechanical ventilation can exacerbate acute lung injury (ALI) due to extrapulmonary sepsis underscoring a potential interactive contribution of common events (sepsis and mechanical ventilation) in critical care, and that a WISP1–TLR4–integrin β5 pathway contributes to this phenomenon. Mechanical ventilation (MTV), that in itself did not cause ALI, exacerbated increases in alveolar-capillary permeability, histopathologic scoring and indices of pulmonary inflammation in mice that previously underwent CLP. We used a two-hit model of cecal ligation and puncture (CLP) followed 12 h later by MTV (10 ml/kg; 6 h) to determine whether otherwise noninjurious MTV enhances CLP-induced ALI.

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