title: The mechanism of development of acute lung injury in lethal endotoxic shock using alpha-galactosylceramide sensitization.
abstract: The mechanism underlying acute lung injury in lethal endotoxic shock induced by administration of lipopolysaccharide (LPS) into alpha-galactosylceramide (alpha-GalCer)-sensitized mice was studied. Sensitization with alpha-GalCer resulted in the increase of natural killer T (NK T) cells and the production of interferon (IFN)-gamma in the lung. The IFN-gamma that was produced induced expression of adhesion molecules, especially vascular cell adhesion molecule-1 (VCAM-1), on vascular endothelial cells in the lung. Anti-IFN-gamma antibody inhibited significantly the VCAM-1 expression in alpha-GalCer-sensitized mice. Very late activating antigen-4-positive cells, as the counterpart of VCAM-1, accumulated in the lung. Anti-VCAM-1 antibody prevented LPS-mediated lethal shock in alpha-GalCer-sensitized mice. The administration of LPS into alpha-GalCer-sensitized mice caused local production of excessive proinflammatory mediators, such as tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6 and nitric oxide. LPS caused microvascular leakage of proteins and cells into bronchoalveolar lavage fluid. Taken together, sensitization with alpha-GalCer was suggested to induce the expression of VCAM-1 via IFN-gamma produced by NK T cells and recruit a number of inflammatory cells into the lung. Further, LPS was suggested to lead to the production of excessive proinflammatory mediators, the elevation of pulmonary permeability and cell death. The putative mechanism of acute lung injury in LPS-mediated lethal shock using alpha-GalCer sensitization is discussed.
authors.affiliation: Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
authors.forename: G
authors.initials: G
authors.lastname: Tumurkhuu
authors.forename: N
authors.initials: N
authors.lastname: Koide
authors.forename: J
authors.initials: J
authors.lastname: Dagvadorj
authors.forename: A
authors.initials: A
authors.lastname: Morikawa
authors.forename: F
authors.initials: F
authors.lastname: Hassan
authors.forename: S
authors.initials: S
authors.lastname: Islam
authors.forename: Y
authors.initials: Y
authors.lastname: Naiki
authors.forename: I
authors.initials: I
authors.lastname: Mori
authors.forename: T
authors.initials: T
authors.lastname: Yoshida
authors.forename: T
authors.initials: T
authors.lastname: Yokochi
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004195:Disease Models, Animal; D005699:Galactosylceramides / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism; D039041:Integrin alpha4beta1 / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008070:Lipopolysaccharides; D008168:Lung / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010539:Permeability; D016133:Polymerase Chain Reaction / Q000379:methods; D012128:Respiratory Distress Syndrome / Q000209:etiology* / Q000276:immunology; D012772:Shock, Septic / Q000150:complications*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D005699:Galactosylceramides; D018836:Inflammation Mediators; D039041:Integrin alpha4beta1; D008070:Lipopolysaccharides; D019010:Vascular Cell Adhesion Molecule-1; C493154:alpha-galactosylceramide; D007371:Interferon-gamma