Enhancement of the endotoxin recognition pathway by ventilation with a large tidal volume in rabbits

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Abstract
Ventilation with a small tidal volume (Vt) is associated with better clinical outcomes than with a large Vt, particularly in critical settings, including acute lung injury. To determine whether Vtinfluences the lipopolysaccaharide (LPS) recognition pathway, we studied CD14 expression in rabbit lungs and the release of TNF-α by cultured alveolar macrophages after 240 min of ventilation with a large (20 ml/kg) vs. a small (5 ml/kg) Vt. We also applied small or large Vtto lungs instilled with 50 μg/kg of LPS. The alveolar macrophages collected after large Vtventilation revealed a 20-fold increase in LPS-induced TNF-α release compared with those collected after small Vtventilation, whereas TNF-α was undetectable without LPS stimulation. In animals ventilated with a large Vt, the expression of CD14 mRNA in whole lung homogenates and the expression of CD14 protein on alveolar macrophages, assessed by immunohistochemistry, were both significantly increased in the absence of LPS stimulation. A large Vtapplied to LPS-instilled lungs increased the pulmonary albumin permeability and TNF-α release into the plasma. These results suggest that mechanical stress caused by a large Vtsensitizes the lungs to endotoxin, a phenomenon that may occur partially via the upregulation of CD14.

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