RGD Reference Report - Graft protective effects of heme oxygenase 1 in mouse tracheal transplant-related obliterative bronchiolitis. - Rat Genome Database

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

Authors: Visner, GA  Lu, F  Zhou, H  Latham, C  Agarwal, A  Zander, DS 
Citation: Visner GA, etal., Transplantation. 2003 Aug 27;76(4):650-6.
RGD ID: 4145412
Pubmed: PMID:12973103   (View Abstract at PubMed)
DOI: DOI:10.1097/01.TP.0000080069.61917.18   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
bronchiolitis obliterans  ISOHmox1 (Mus musculus)4145412; 4145412 RGD 
bronchiolitis obliterans  IMP 4145412 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hmox1  (heme oxygenase 1)

Genes (Mus musculus)
Hmox1  (heme oxygenase 1)

Genes (Homo sapiens)
HMOX1  (heme oxygenase 1)


Additional Information