Graft protective effects of heme oxygenase 1 in mouse tracheal transplant-related obliterative bronchiolitis.

Abstract

BACKGROUND:

Heme oxygenase (HO)-1, long believed to be a cytoprotective protein, has recently been identified as a graft survival gene. This study evaluates the role of HO-1 in a murine heterotopic tracheal allograft model for obliterative bronchiolitis.

METHODS:

Mice with deficient or experimentally enhanced HO-1 expression underwent subcutaneous implantation of murine tracheal isografts and allografts. Grafts were excised after 9, 16, or 21 days and evaluated by histologic examination, immunohistochemistry for HO-1 and interleukin (IL)-10 proteins, and terminal deoxynucleotide transferase-mediated dUTP nick-end labeling. To evaluate the relationships between IL-10 and HO-1, the effects of modulation of HO-1 expression on IL-10 expression were evaluated and HO-1 expression was examined in tracheal transplants from IL-10 null mice.

RESULTS:

Isografts demonstrated normal histology with minimal HO-1 staining, whereas allografts showed features of human airway rejection (loss of respiratory epithelium, luminal granulation tissue, lymphocytic tracheitis) with increased HO-1 staining in macrophages and mesenchymal cells. HO-1-deficient mice demonstrated a more rapid progression of the tracheal allograft injury as compared with control allografts, and this was associated with a decrease in the anti-inflammatory cytokine, IL-10. Tracheal transplants using IL-10-deficient mice also resulted in a more severe injury, and this was accompanied by a decrease in HO-1 staining.

CONCLUSIONS:

HO-1 protein expression is increased in murine heterotopic airway rejection, and deficiency of HO-1 accelerates the development of the obliterative bronchiolitis-like lesion. IL-10 protein expression parallels expression of HO-1, suggesting that IL-10 may participate in the genesis of HO-1's effects on the inflammatory processes triggered by allotransplantation.

• Authors: Gary A Visner, Fuhua Lu, Hailan Zhou, Christopher Latham, Anupam Agarwal, Dani S Zander
• Journal: Transplantation (Transplantation) Vol. 76 Issue 4 Pg. 650-6 (Aug 27 2003) ISSN: 0041-1337 [Print] United States
• PMID: 12973103 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Membrane Proteins
• Interleukin-10
• Collagen
• Heme Oxygenase (Decyclizing)
• Heme Oxygenase-1
• Hmox1 protein, mouse

Topics

• Animals
• Bronchiolitis Obliterans (prevention & control)
• Collagen (metabolism)
• Graft Rejection
• Heme Oxygenase (Decyclizing) (analysis, physiology)
• Heme Oxygenase-1
• In Situ Nick-End Labeling
• Interleukin-10 (physiology)
• Membrane Proteins
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Trachea (enzymology, transplantation)
• Transplantation, Homologous