Alteration of fibroblast architecture and loss of Basal lamina apertures in human emphysematous lung

Am J Respir Crit Care Med. 2006 Mar 15;173(6):632-8. doi: 10.1164/rccm.200509-1434OC. Epub 2006 Jan 13.


Rationale: In normal human lung, single alveolar fibroblasts link capillary endothelium to type 2 pneumocytes through apertures in the endothelial and epithelial basal laminae. These fibroblasts are hypothesized to play a role in cellular communication between the endothelium and epithelium and are positioned to provide leukocytes a surface on which they may migrate through the interstitium.

Objectives: To determine whether fibroblasts link the endothelium to the epithelium in emphysematous lung and to compare basal lamina aperture frequency with previously published results.

Methods: We performed transmission electron microscopy serial section three-dimensional reconstructions of emphysematous regions of human alveolar wall and a quantitative analysis of basal lamina apertures beneath 403 type 2 pneumocytes.

Measurements and main results: Our three-dimensional reconstruction demonstrated that the fibroblasts subtending type 2 pneumocytes in emphysematous lung no longer link these epithelial cells to the capillary endothelium through basal lamina apertures. Basal lamina apertures may be absent below some type 2 pneumocytes. Our morphometric analysis showed that their frequency and area beneath type 2 pneumocytes is significantly reduced in emphysematous regions when compared with nonemphysematous regions of matched control lung.

Conclusions: We conclude that the endothelial/fibroblast/epithelial linkage is disrupted in emphysematous human lungs and postulate this disruption may disturb leukocyte migration and account for their accumulation in the alveolar interstitium of emphysematous lung tissue.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Basement Membrane / ultrastructure*
  • Fibroblasts / ultrastructure*
  • Humans
  • Image Processing, Computer-Assisted
  • In Vitro Techniques
  • Microscopy, Electron, Transmission
  • Pulmonary Alveoli / ultrastructure*
  • Pulmonary Emphysema / pathology*
  • Severity of Illness Index