title: Various adhesion molecules impair microvascular leukocyte kinetics in ventilator-induced lung injury.
abstract: 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.
authors.affiliation: Department of Medicine, Kitasato Institute Hospital, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8642, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Miyao
authors.forename: Yukio
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Kei
authors.initials: K
authors.lastname: Takeshita
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Kudo
authors.forename: Makoto
authors.initials: M
authors.lastname: Ishii
authors.forename: Rika
authors.initials: R
authors.lastname: Hiraoka
authors.forename: Kazumi
authors.initials: K
authors.lastname: Nishio
authors.forename: Takuya
authors.initials: T
authors.lastname: Tamatani
authors.forename: Shinji
authors.initials: S
authors.lastname: Sakamoto
authors.forename: Makoto
authors.initials: M
authors.lastname: Suematsu
authors.forename: Harukuni
authors.initials: H
authors.lastname: Tsumura
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Ishizaka
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamaguchi
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000502:physiology*; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007962:Leukocytes / Q000166:cytology / Q000502:physiology*; D008171:Lung Diseases / Q000209:etiology* / Q000503:physiopathology*; D008297:Male; D008833:Microcirculation / Q000502:physiology*; D018613:Microscopy, Confocal; D009504:Neutrophils / Q000502:physiology; D019007:P-Selectin / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*; D012122:Ventilators, Mechanical / Q000009:adverse effects*
chemical_list: D019007:P-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1