Journal
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
Volume 286, Issue 6, Pages L1114-L1121Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.00296.2003
Keywords
acute lung injury; ventilator-induced lung injury
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Funding
- NHLBI NIH HHS [HL-30542] Funding Source: Medline
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Ventilation with a small tidal volume (V-t) is associated with better clinical outcomes than with a large V-t, particularly in critical settings, including acute lung injury. To determine whether Vt influences the lipopolysaccaharide (LPS) recognition pathway, we studied CD14 expression in rabbit lungs and the release of TNF-alpha by cultured alveolar macrophages after 240 min of ventilation with a large ( 20 ml/kg) vs. a small ( 5 ml/kg) V-t. We also applied small or large Vt to lungs instilled with 50 mug/kg of LPS. The alveolar macrophages collected after large V-t ventilation revealed a 20-fold increase in LPS-induced TNF-alpha release compared with those collected after small V-t ventilation, whereas TNF-alpha was undetectable without LPS stimulation. In animals ventilated with a large V-t, 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 V-t applied to LPS-instilled lungs increased the pulmonary albumin permeability and TNF-alpha release into the plasma. These results suggest that mechanical stress caused by a large Vt sensitizes the lungs to endotoxin, a phenomenon that may occur partially via the upregulation of CD14.
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