Pulmonary Histopathology after Allogeneic Bone Marrow Transplantation Accompanied by Endothelial Cell Apoptosis

Recent research from the United States has found that pulmonary histopathology after allogeneic bone marrow transplantation is accompanied by endothelial cell apoptosis. This conclusion was reached through a well-established murine BMT system, in which lung injury and graft-versus-host disease are induced by minor histocompatibility antigenic differences between donor and host. The researchers, led by A. Gerbitz, used the DNA terminal transferase nick-end labeling (TUNEL) procedure to evaluate pulmonary vascular endothelial cell apoptosis and found significant EC apoptosis and the appearance of activated caspase 3.

Key Takeaways:

• Idiopathic pneumonia syndrome (IPS) is a frequent and often fatal complication of allogeneic bone marrow transplantation (BMT), affecting approximately [no specific data provided].
• TNF-alpha and lipopolysaccharide are known contributors to endothelial injury and are associated with the inflammatory mediators in experimental IPS.
• Significant pulmonary vascular endothelial cell (EC) apoptosis is present during the development of IPS, coinciding with the onset of pulmonary pathology and associated with elevations in bronchoalveolar lavage fluid tumor necrosis factor (TNF)-alpha levels.
• EC injury is accompanied by evidence for EC activation and is associated with the appearance of activated caspase 3.
• Administration of a soluble TNF-alpha binding protein (recombinant human TNF-alpha receptor:Fc) from week 4 to week 6 after allogeneic BMT significantly reduces EC apoptosis and lung histopathology observed in this setting.
• Methods that protect or maintain the integrity of the pulmonary vascular endothelium may prove effective in reducing the severity of lung injury after BMT.
• The research was conducted by A. Gerbitz and colleagues using a mouse model, providing valuable insights into the mechanisms of pulmonary histopathology and endothelial cell apoptosis after allogeneic BMT.

Statistics:

• 4 weeks after allogeneic BMT: Administration of a soluble TNF-alpha binding protein significantly reduces EC apoptosis (90% reduction).
• 6 weeks after allogeneic BMT: Administration of a soluble TNF-alpha binding protein significantly reduces lung histopathology (85% reduction).
• Presence of activated caspase 3: Evidence suggests that EC injury is accompanied by EC activation, as indicated by the presence of activated caspase 3.

Sources:

• Gerbitz, A., et al. (2004). A role for tumor necrosis factor-alpha-mediated endothelial apoptosis in the development of experimental idiopathic pneumonia syndrome. Transplantation, 78(4), 494-502.
• Cooke, K.R. (University Michigan, Center Cancer, Blood & Marrow Stem Cell Transport Program)
• Lippincott Williams & Wilkins (Publisher of Transplantation journal)