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

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.

Human alveolar wall fibroblasts directly link epithelial type 2 cells to capillary endothelium.

Alveolar wall fibroblasts directly link type 2 (T2) pneumocytes to capillary endothelium through apertures in their respective basal laminae in rabbit lung. These fibroblasts provide a bridge from the capillary to the airway lumen along which leukocytes may migrate without disrupting extracellular matrix. Normal human lungs were examined by transmission electron microscopy and serial section 3D reconstruction. We found contacts between fibroblasts and T2 pneumocytes and between fibroblasts and type 1 pneumocytes that occur at holes in the epithelial basal lamina. The same fibroblast also made contact with pericytes and endothelial cells through similar apertures. A survey of 41 T2 pneumocytes revealed that 54% of T2 pneumocytes had at least one gap in their basal lamina. A morphometric analysis showed these gaps occupied approximately 5.58 +/- 1.51% (mean +/- SE) of the area underneath T2 pneumocytes. We conclude that a population of single fibroblasts link T2 pneumocytes to adjacent capillary endothelial cells in alveolar walls of human lung. We propose that fibroblasts are organized to maintain communication between epithelium and mesenchyme and to provide directional information to migrating leukocytes.