Various adhesion molecules impair microvascular leukocyte kinetics in ventilator-induced lung injury

Naoki Miyao, Yukio Suzuki, Kei Takeshita, Hiroyasu Kudo, Makoto Ishii, Rika Hiraoka, Kazumi Nishio, Takuya Tamatani, Shinji Sakamoto, Makoto Suematsu, Harukuni Tsumura, Akitoshi Ishizaka, Kazuhiro Yamaguchi

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37 Citations (Scopus)


Although the endothelial expression of various adhesion molecules substantially differs between pulmonary microvessels, their importance for neutrophil and lymphocyte sequestration in ventilator-induced lung injury (VILI) has not been systematically analyzed. We investigated the kinetics of polymorphonuclear cells (PMN) and mononuclear cells (MN) in the acinar microcirculation of the isolated rat lung with VILI by real-time confocal laser fluorescence microscopy, with or without inhibition of ICAM-1, VCAM-1, or P-selectin by monoclonal antibodies (MAb). Adhesion molecules in each microvessel were estimated by intravital fluorescence microscopy or immunohistochemical staining. In high tidal volume-ventilated lungs, 1) ICAM-1, VCAM-1, and P-selectin were differently upregulated in venules, arterioles, and capillaries; 2) venular PMN rolling was improved by inhibition of ICAM-1, VCAM-1, or P-selectin, whereas arteriolar PMN rolling was improved by ICAM-1 or VCAM-1 inhibition; 3) capillary PMN entrapment was ameliorated only by anti-ICAM-1 MAb; and 4) MN rolling in venules and arterioles and MN entrapment in capillaries were improved by ICAM-1 and VCAM-1 inhibition. In conclusion, the contribution of endothelial adhesion molecules to abnormal leukocyte behavior in VILI-injured microcirculation is microvessel and leukocyte specific. ICAM-1- and VCAM-1-dependent, but P-selectin-independent, arteriolar PMN rolling, which is expected to reflect the initial stage of tissue injury, should be taken as a phenomenon unique to ventilator-associated lung injury.

Original languageEnglish
Pages (from-to)L1059-L1068
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number6
Publication statusPublished - 2006 Jun


  • Adhesion
  • Lymphocyte
  • Neutrophil
  • Rolling

ASJC Scopus subject areas

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


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