Enhancement of the endotoxin recognition pathway by ventilation with a large tidal volume in rabbits.
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 V(t) 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 V(t) to lungs instilled with 50 microg/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 V(t) sensitizes the lungs to endotoxin, a phenomenon that may occur partially via the upregulation of CD14.
Moriyama
Kiyoshi
K
Department of Anesthesiology, School of Medicine, Keio University, Tokyo, Japan.
Ishizaka
Akitoshi
A
Nakamura
Morio
M
Kubo
Hiroshi
H
Kotani
Toru
T
Yamamoto
Shinichi
S
Ogawa
Eileen N
EN
Kajikawa
Osamu
O
Frevert
Charles W
CW
Kotake
Yoshifumi
Y
Morisaki
Hiroshi
H
Koh
Hidefumi
H
Tasaka
Sadatomo
S
Martin
Thomas R
TR
Takeda
Junzo
J
D000418:Albumins / Q000378:metabolism; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002478:Cells, Cultured; D015870:Gene Expression; D007958:Leukocyte Count; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000166:cytology / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000166:cytology; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D012121:Respiration, Artificial / Q000009:adverse effects*; D012128:Respiratory Distress Syndrome / Q000209:etiology* / Q000276:immunology / Q000378:metabolism*; D013990:Tidal Volume; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
D000418:Albumins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha