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

Kiyoshi Moriyama, Akitoshi Ishizaka, Morio Nakamura, Hiroshi Kubo, Toru Kotani, Shinichi Yamamoto, Eileen N. Ogawa, Osamu Kajikawa, Charles W. Frevert, Yoshifumi Kotake, Hiroshi Morisaki, Hidefumi Koh, Sadatomo Tasaka, Thomas R. Martin, Junzo Takeda

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)L1114-L1121
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number6 30-6
Publication statusPublished - 2004 Jun


  • Acute lung injury
  • Ventilator-induced lung injury

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology


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