Critical roles of capillary endothelial cells for alveolar remodeling in nonspecific and usual interstitial pneumonias Journal Article


Authors: Tachihara, A.; Jin, E.; Matsuoka, T.; Ghazizadeh, M.; Yoshino, S.; Takemura, T.; Travis, W. D.; Kawanami, O.
Article Title: Critical roles of capillary endothelial cells for alveolar remodeling in nonspecific and usual interstitial pneumonias
Abstract: To characterize the relationship between angiogenesis factors and alveolar remodeling in interstitial lung diseases, we examined alveolar capillary endothelial cells in the normal lung (n=5) and in lungs with nonspecific interstitial pneumonia (NSIP) (n=4) or usual interstitial pneumonia (UIP) (n=6) using immunofluorescence staining for thrombmodulin and von Willebrand factor (vWF). With three-dimensional images of alveolar capillaries, the diameter of capillary tubes and their branching frequency per unit length were determined to define rearrangement of the capillary meshwork. Alveolar capillary endothelial cells in normal lungs expressed surface thrombomodulin, and those in lungs with cellular NSIP often showed coexpression of surface thrombmodulin and cytoplasmic vWF. In the alveolar septa of fibrotic NSIP and UIP, capillary endothelial cells demonstrated vWF in only the cytoplasm. Capillary branching frequencies in NSIP and UIP were decreased to 45% and 22%, respectively, of the normal level (p<0.002). Compared with normal lungs, in NSIP and UIP lungs alveolar capillaries containing TUNEL-positive endothelial cells (p<0.05) showed increases of 3.6-fold and 4.3-fold, respectively, indicating a close correlation between endothelial cell apoptosis and remodeling of alveolar capillary frameworks. The analysis of mRNA expression of vascular endothelial growth factors (VEGF) and their receptors (VEGFR1 and VEGFR2) showed a significant decrease in each VEGF isoform and in VEGFR2 mRNA in representative alveolar wall tissues microdissected from the normal, NSIP, and UIP lungs. These results suggest that decreased expression of VEGF mRNA is associated with a reduction in the number of capillary tubes via endothelial cell apoptosis that possibly results in alveolar remodeling in NSIP and UIP. However, whether VEGF is related to fibroblastic activation in the interstitial matrix remains unclear.
Keywords: adult; clinical article; controlled study; human tissue; middle aged; vascular endothelial growth factor a; apoptosis; immunofluorescence; vasculotropin receptor 2; vascular endothelial growth factor receptor-2; endothelium cell; endothelial cells; fluorescent antibody technique; antigens; messenger rna; rna, messenger; three dimensional imaging; vascular endothelial growth factor receptor-1; vasculotropin receptor 1; microdissection; thrombomodulin; interstitial pneumonia; usual interstitial pneumonia; capillary endothelium; nonspecific interstitial pneumonia; lung diseases, interstitial; lung alveolus wall; von willebrand factor; alveolar capillary remodeling; pulmonary alveoli
Journal Title: Journal of Nippon Medical School
Volume: 73
Issue: 4
ISSN: 1345-4676
Publisher: Nippon Ika Daigaku Igakkai,Medical Association of Nippon Medical School  
Date Published: 2006-08-01
Start Page: 203
End Page: 213
Language: English
DOI: 10.1272/jnms.73.203
PUBMED: 16936446
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 4" - "Export Date: 4 June 2012" - "CODEN: NIDZA" - "Source: Scopus"
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  1. William D Travis
    743 Travis