Epithelial tenascin predicts obliterative airway disease.
BACKGROUND
Epithelial cell injury, inflammation, fibrosis and airway obliteration result in remodeling of terminal bronchi in post-transplant obliterative bronchiolitis. Tenascin as an extracellular matrix glycoprotein is expressed in several remodeling processes.


METHODS
Heterotopic bronchial allografts of pigs were studied to assess tenascin expression during development of post-transplant obliterative bronchiolitis. A total of 157 allografts or autograft controls were serially obtained 2 to 28 days after transplantation and processed for histology and immunocytochemistry for tenascin, CD4, CD8 and macrophages. Epithelial tenascin index was calculated by multiplying the percentage of positive cells by the grade of tenascin intensity (1 to 3).


RESULTS
Epithelial tenascin expression occurred during the initial ischemic damage to the respiratory epithelium. After partial recovery and before total epithelial loss and subsequent airway obliteration, tenascin expression peaked in allografts (p < 0.001). Epithelial tenascin index on Day 7 was predictive of subsequent epithelial damage, bronchial wall inflammation and the number of (CD4(+) and CD8(+)) cells, fibroproliferation, and obliteration of the bronchial lumen (R > or = 0.47, p < or = 0.01). Tenascin expression in the bronchial wall was more intense in allografts (p < 0.001), paralleling proliferation of fibroblasts and influx of inflammatory cells, and was predictive of inflammatory alterations also in the early obliterative lesions (R > or = 0.45, p < 0.05). Expression decreased during maturation of fibrosis (p < 0.05).


CONCLUSIONS
Epithelial tenascin was predictive of features observed in post-transplant obliterative bronchiolitis, demonstrating a role for tenascin in the development of obliterative bronchiolitis. Tenascin may have relevant properties in serving as a clinical marker for early obliterative bronchiolitis.
Päiväniemi
Outi E
OE
Department of Cardiothoracic Surgery, Helsinki University Hospital, Helsinki, Finland.
Maasilta
Paula K
PK
Alho
Hanni S
HS
Vainikka
Tiina L S
TL
Salminen
Ulla-Stina
US
D000818:Animals; D001980:Bronchi / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation*; D001989:Bronchiolitis Obliterans / Q000209:etiology* / Q000473:pathology; D001991:Bronchitis / Q000209:etiology / Q000473:pathology; D049109:Cell Proliferation; D005347:Fibroblasts / Q000473:pathology; D005355:Fibrosis; D007150:Immunohistochemistry; D016377:Organ Transplantation / Q000009:adverse effects; D011183:Postoperative Complications; D011184:Postoperative Period; D011237:Predictive Value of Tests; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology; D013552:Swine; D019063:Tenascin / Q000378:metabolism*; D013997:Time Factors; D014184:Transplantation, Homologous
D019063:Tenascin