TY - JOUR
T1 - Enhancement of the endotoxin recognition pathway by ventilation with a large tidal volume in rabbits
AU - Moriyama, Kiyoshi
AU - Ishizaka, Akitoshi
AU - Nakamura, Morio
AU - Kubo, Hiroshi
AU - Kotani, Toru
AU - Yamamoto, Shinichi
AU - Ogawa, Eileen N.
AU - Kajikawa, Osamu
AU - Frevert, Charles W.
AU - Kotake, Yoshifumi
AU - Morisaki, Hiroshi
AU - Koh, Hidefumi
AU - Tasaka, Sadatomo
AU - Martin, Thomas R.
AU - Takeda, Junzo
PY - 2004/6/1
Y1 - 2004/6/1
N2 - 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 V t influences the lipopolysaccaharide (LPS) recognition pathway, we studied CD 14 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 Vt to lungs instilled with 50 μg/kg of LPS. The alveolar macrophages collected after large Vt ventilation revealed a 20-fold increase in LPS-induced TNF-α release compared with those collected after small Vt ventilation, 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 V t applied 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 Vt sensitizes the lungs to endotoxin, a phenomenon that may occur partially via the upregulation of CD14.
AB - 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 V t influences the lipopolysaccaharide (LPS) recognition pathway, we studied CD 14 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 Vt to lungs instilled with 50 μg/kg of LPS. The alveolar macrophages collected after large Vt ventilation revealed a 20-fold increase in LPS-induced TNF-α release compared with those collected after small Vt ventilation, 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 V t applied 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 Vt sensitizes the lungs to endotoxin, a phenomenon that may occur partially via the upregulation of CD14.
KW - Acute lung injury
KW - Ventilator-induced lung injury
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U2 - 10.1152/ajplung.00296.2003
DO - 10.1152/ajplung.00296.2003
M3 - Article
C2 - 14633514
AN - SCOPUS:2442694185
VL - 286
SP - L1114-L1121
JO - American Journal of Physiology - Lung Cellular and Molecular Physiology
JF - American Journal of Physiology - Lung Cellular and Molecular Physiology
SN - 1040-0605
IS - 6 30-6
ER -