Evolution of endotoxin-induced lung injury in the rat beyond the acute phase

Pathobiology. 2004;71(2):59-69. doi: 10.1159/000074418.


Objectives: Intratracheal endotoxin in rats causes acute lung injury. Here we have addressed the cellular physiopathology of lung recovery from that injury.

Methods: The lungs of 5 untreated rats and rats treated with intratracheal endotoxin from 2, 3, 5, 8 (5 rats each) and 15 days (2 rats) were studied by light and electron microscopy and immunohistochemistry.

Results: In the acute phase there was a reduction in the aerated spaces (p < 0.01); diffuse infiltration of granulocytes and macrophages; hyperplasia of type-II pneumocytes, and hypertrophy of interstitial cells. Aerated spaces improved during recovery. In the early recovery phase (3-8 days) the compartmentalization of infiltrating cells varied significantly (p < 0.01): macrophages remained widespread while neutrophils were inside blood vessels. Many pneumocytes were intermediate between type-I and type-II cells. In the late recovery phase (15 days) the infiltrate disappeared; myofibroblasts were significantly more than previously (p < 0.01) and extracellular matrix was abundant; type-II pneumocytes contained non-lamellated lipid inclusions.

Conclusions: Macrophages play a pivotal role in the damage-repair processes of the lung following endotoxin injury, leading to an increase in extracellular matrix, differentiation of myofibroblasts and altered secretion of surfactant by newly differentiated type-II pneumocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chronic Disease
  • Disease Models, Animal
  • Endotoxins / toxicity*
  • Epithelial Cells / pathology
  • Extracellular Matrix / pathology
  • Fibroblasts / pathology
  • Granulocytes / immunology
  • Immunohistochemistry
  • Lung / drug effects*
  • Lung / pathology*
  • Lung / ultrastructure
  • Microscopy, Electron
  • Pulmonary Surfactants / metabolism
  • Rats
  • Respiratory Distress Syndrome / immunology
  • Respiratory Distress Syndrome / pathology*
  • Respiratory Distress Syndrome / physiopathology*


  • Endotoxins
  • Pulmonary Surfactants