Endothelial cells as early sensors of pulmonary interstitial edema

Rossella Daffara, Laura Botto, Egidio Beretta, Elena Conforti, Andrea Faini, Paola Palestini, Giuseppe Miserocchi

Research output: Contribution to journalArticlepeer-review


We studied responses of endothelial and epithelial cells in the thin portion of the air-blood barrier to a rise in interstitial pressure caused by an increase in extravascular water (interstitial edema) obtained in anesthetized rabbits receiving saline infusion (0.5 ml·kg -1·min -1 for 3 h). We obtained morphometric analyses of the cells and of their microenvironment (electron microscopy); furthermore, we also studied in lung tissue extracts the biochemical alterations of proteins responsible for signal transduction (PKC, caveolin-1) and cell-cell adhesion (CD31) and of proteins involved in membrane-to-cytoskeleton linkage (α-tubulin and β-tubulin). In endothelial cells, we observed a folding of the plasma membrane with an increase in cell surface area, a doubling of plasmalemma vesicular density, and an increase in cell volume. Minor morphological changes were observed in epithelial cells. Edema did not affect the total plasmalemma amount of PKC, β-tubulin, and caveolin-1, but α-tubulin and CD-31 increased. In edema, the distribution of these proteins changed between the detergent-resistant fraction of the plasma membrane (DRF, lipid microdomains) and the rest of the plasma membrane [high-density fractions (HDFs)]. PKC and tubulin isoforms shifted from the DRF to HDFs in edema, whereas caveolin-1 increased in DRF at the expense of a decrease in phosphorylated caveolin-1. The changes in cellular morphology and in plasma membrane composition suggest an early endothelial response to mechanical stimuli arising at the interstitial level subsequently to a modest (∼5%) increase in extravascular water.

Original languageEnglish
Pages (from-to)1575-1583
Number of pages9
JournalJournal of Applied Physiology
Issue number4
Publication statusPublished - Oct 2004


  • Air-blood barrier
  • Mechanotransduction
  • Morphometry
  • Plasma membrane proteins
  • Pulmonary interstitial pressure

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation


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