Localization of insulin-like growth factor-I in lung tissues of patients with fibroproliferative acute respiratory distress syndrome.
Insulin-like growth factor-I (IGF-I) is elevated in human fibrotic lung diseases and in animal models of pulmonary fibrosis, implicating IGF-I in the pathogenesis of fibrotic lung disease. We questioned whether IGF-I protein levels were enhanced in fibroproliferative acute respiratory distress syndrome (FP-ARDS). Serial lung tissue sections from a biopsy database were immunohistochemically stained for IGF-I, IGF-I receptor, CD68, alpha-smooth muscle actin, collagens I and III, and proliferating cell nuclear antigen. Our results show enhanced staining of IGF-I and IGF-I receptor, collagens I and III, smooth muscle actin, CD68, and proliferating cell nuclear antigen in FP-ARDS compared with control lung sections. In FP-ARDS specimens, prominent staining of IGF-I and IGF-I receptor was seen in alveolar and interstitial macrophages as well as in a variety of mesenchymal cells. There was a correlation between IGF-I staining and CD68-positive cells, suggesting macrophages as a potential source of the IGF-I protein present in lungs. IGF-I also correlated with enhanced collagen I, collagen III, and proliferating cell nuclear antigen immunoreactivity, suggesting that IGF-I may play a role in the extracellular matrix protein deposition and cellular proliferation seen in the lungs of individuals with FP-ARDS. Our results indicate that IGF-I is increased in FP-ARDS and may be an important mediator in the progression of acute lung injury to FP-ARDS.
Krein
Peter M
PM
Department of Medicine, University of Calgary, Health Sciences Center, Calgary, Alberta, Canada.
Sabatini
Peter J B
PJ
Tinmouth
William
W
Green
Francis H Y
FH
Winston
Brent W
BW
D000199:Actins / Q000032:analysis; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D024042:Collagen Type I / Q000032:analysis; D024061:Collagen Type III / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008168:Lung / Q000737:chemistry*; D016676:Macrophages, Alveolar / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D011285:Pregnenolone Carbonitrile / Q000032:analysis; D017526:Receptor, IGF Type 1 / Q000032:analysis; D012128:Respiratory Distress Syndrome / Q000378:metabolism*; D000097382:CD68 Molecule
D000199:Actins; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D024042:Collagen Type I; D024061:Collagen Type III; D007334:Insulin-Like Growth Factor I; D011285:Pregnenolone Carbonitrile; D017526:Receptor, IGF Type 1; C067980:CD68 antigen, human; D000097382:CD68 Molecule