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Alteration of Fibroblast Architecture and Loss of Basal Lamina Apertures in Human Emphysematous Lung

The James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research/Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia

Correspondence and requests for reprints should be addressed to David C. Walker, Ph.D., James Hogg iCAPTURE Centre Room 166, Burrard Building, 1081 Burrard Street (St Paul's Hospital), Vancouver, BC, V6Z 1Y6 Canada. E-mail: dwalker{at}mrl.ubc.ca

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.

Key Words: basal lamina apertures • emphysema • fibroblasts • leukocyte migration • transmission electron microscopy

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