Thus, the overall hypotheses of this study were that: prolonged ventilation with otherwise noninjurious moderate VT exacerbates ALI in extrapulmonary sepsis; WISP1 and integrin β5 contribute to this two-hit model (i.e., CLP + MTV); and TLR4 is central to the WISP1–TLR4–integrin β5 proinflammatory pathway. Here, CCN4 is linked to acute respiratory distress syndrome.