Cytokine and adhesion molecule requirements for lung injury induced by anti-glomerular basement membrane antibody.

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 TNF alpha and IL-1. Experiments employing blocking antibodies to adhesion molecules demonstrated requirements for the beta 1 integrin VLA-4, beta 2 integrins LFA-1 and Mac-1, and L-selection. The endothelial cell adhesion molecules, E-selectin and ICAM-1, were also required for the full development of lung injury. Inhibition of TNF alpha 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.

• Authors: M S Mulligan, A B Lentsch, T P Shanley, M Miyasaka, K J Johnson, P A Ward
• Journal: Inflammation (Inflammation) Vol. 22 Issue 4 Pg. 403-17 (Aug 1998) ISSN: 0360-3997 [Print] United States
• PMID: 9675611 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies
• Antibodies, Blocking
• Antibodies, Monoclonal
• Cell Adhesion Molecules
• Cytokines
• Immunoglobulin G
• Integrin alpha4beta1
• Integrins
• Interleukin-1
• Lymphocyte Function-Associated Antigen-1
• Macrophage-1 Antigen
• Receptors, Lymphocyte Homing
• Tumor Necrosis Factor-alpha
• L-Selectin
• Complement System Proteins

Topics

• Animals
• Anti-Glomerular Basement Membrane Disease (etiology, immunology, pathology)
• Antibodies (administration & dosage)
• Antibodies, Blocking (administration & dosage)
• Antibodies, Monoclonal (administration & dosage)
• Basement Membrane (immunology)
• Cell Adhesion Molecules (metabolism)
• Complement System Proteins (metabolism)
• Cytokines (antagonists & inhibitors, metabolism)
• Disease Models, Animal
• Humans
• Immunoglobulin G (administration & dosage)
• Integrin alpha4beta1
• Integrins (antagonists & inhibitors, metabolism)
• Interleukin-1 (antagonists & inhibitors, metabolism)
• Kidney Glomerulus (immunology)
• L-Selectin (metabolism)
• Lung (immunology)
• Lung Injury
• Lymphocyte Function-Associated Antigen-1 (metabolism)
• Macrophage-1 Antigen (metabolism)
• Male
• Neutrophils (immunology)
• Rats
• Receptors, Lymphocyte Homing (antagonists & inhibitors, metabolism)
• Sheep
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, metabolism)