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Cytokine and Adhesion Molecule Requirements for Lung Injury Induced by Anti-Glomerular Basement Membrane Antibody

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Abstract

Acute hemorrhagic lung injury occurs in humans with anti-GBM antibody (Goodpasture's syndrome), however, the mechanism of this injury is still largely unknown. To date, treatment has been confined to steroids and plasmaphoresis. Infusion of anti-GBM antibody into rats caused lung injury with intra-alveolar hemorrhage and intrapulmonary accumulation of neutrophils. Lung injury was dependent on the presence of neutrophils and complement and required both TNFα and IL-1. Experiments employing blocking antibodies to adhesion molecules demonstrated requirements for the β1 integrin VLA-4, β2 integrins LFA-1 and Mac-1, and L-selectin. The endothelial cell adhesion molecules, E-selectin and ICAM-1, were also required for the full development of lung injury. Inhibition of TNFα or IL-1 or adhesion molecules reduced both lung injury and tissue neutrophil accumulation. Thus, this study underscores cytokine and adhesion molecule requirements for neutrophil mediated injury in lung and kidney caused by anti-GBM, suggesting potential targets for the treatment of Goodpasture's syndrome in humans.

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Authors and Affiliations

  1. Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, 48109

    Michael S. Mulligan, Alex B. Lentsch, Thomas P. Shanley, Kent J. Johnson & Peter A. Ward

  2. Department of Bioregulation, Osaka University Medical School, Japan

    Masayuki Miyasaka

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  1. Michael S. Mulligan
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  2. Alex B. Lentsch
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  4. Masayuki Miyasaka
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Mulligan, M.S., Lentsch, A.B., Shanley, T.P. et al. Cytokine and Adhesion Molecule Requirements for Lung Injury Induced by Anti-Glomerular Basement Membrane Antibody. Inflammation 22, 403–417 (1998). https://doi.org/10.1023/A:1022372900175

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