Inflammation

, Volume 22, Issue 4, pp 403–417

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

  • Michael S. Mulligan
  • Alex B. Lentsch
  • Thomas P. Shanley
  • Masayuki Miyasaka
  • Kent J. Johnson
  • Peter A. Ward
Article

DOI: 10.1023/A:1022372900175

Cite this article as:
Mulligan, M.S., Lentsch, A.B., Shanley, T.P. et al. Inflammation (1998) 22: 403. doi:10.1023/A:1022372900175

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.

Copyright information

© Plenum Publishing Corporation 1998

Authors and Affiliations

  • Michael S. Mulligan
    • 1
  • Alex B. Lentsch
    • 1
  • Thomas P. Shanley
    • 1
  • Masayuki Miyasaka
    • 2
  • Kent J. Johnson
    • 1
  • Peter A. Ward
    • 1
  1. 1.Department of PathologyUniversity of Michigan Medical SchoolAnn Arbor
  2. 2.Department of BioregulationOsaka University Medical SchoolJapan