The mechanism of development of acute lung injury in lethal endotoxic shock using α-galactosylceramide sensitization

G. Tumurkhuu, N. Koide, J. Dagvadorj, A. Morikawa, F. Hassan, S. Islam, Y. Naiki, I. Mori, T. Yoshida, T. Yokochi

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29 Citations (Scopus)

Abstract

The mechanism underlying acute lung injury in lethal endotoxic shock induced by administration of lipopolysaccharide (LPS) into α- galactosylceramide (α-GalCer)-sensitized mice was studied. Sensitization with α-GalCer resulted in the increase of natural killer T (NK T) cells and the production of interferon (IFN)-γ in the lung. The IFN-γ 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-γ antibody inhibited significantly the VCAM-1 expression in α-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 α-GalCer-sensitized mice. The administration of LPS into α-GalCer-sensitized mice caused local production of excessive proinflammatory mediators, such as tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and nitric oxide. LPS caused microvascular leakage of proteins and cells into bronchoalveolar lavage fluid. Taken together, sensitization with α-GalCer was suggested to induce the expression of VCAM-1 via IFN-γ 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 α-GalCer sensitization is discussed.

Original languageEnglish
Pages (from-to)182-191
Number of pages10
JournalClinical and Experimental Immunology
Volume152
Issue number1
DOIs
Publication statusPublished - 04-2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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