Interaction of rat alveolar macrophages with pulmonary epithelial cells following exposure to lipopolysaccharide

Arch Toxicol. 1996;70(3-4):230-6. doi: 10.1007/s002040050265.


Because both alveolar macrophages and pulmonary epithelial cells are primary target cells of inhaled endotoxin, it is of interest to study the interaction of alveolar macrophages with epithelial cells following exposure to lipopolysaccharide (LPS). Repeated bronchoalveolar lavage suggested that rat alveolar macrophages became adhesive to epithelial cells in response to intratracheally instilled LPS at 0.5 h post-exposure in vivo. Adherence of alveolar macrophages to SV40T2 (rat type II pulmonary epithelial cells transformed by SV40) was also increased following 0.5-h stimulation with LPS in vitro. The adherence was increased with dose and reached a plateau at 2 micrograms/ml LPS. The transepithelial resistance of the SV40T2 monolayer was decreased by coculture with macrophages in the presence of LPS for 4 h. The transepithelial resistance was not changed by exposure of SV40T2 alone to LPS or conditioned medium obtained from LPS-stimulated macrophages, suggesting that the intercellular interaction between alveolar macrophages and epithelial cells or unstable products of LPS-exposed alveolar macrophages was associated with the decrease in transepithelial resistance. Following the decrease in transepithelial resistance, lysis of SV40T2 was observed in the LPS-exposed coculture system. However, the lysis of SV40T2 did not occur until 12 h after the addition of LPS, indicating that the junctional change of the monolayer preceded cell death in SV40T2. Cytotoxicity of LPS-stimulated macrophages was significantly reduced by NG-monomethyl-L-arginine (NMMA), an inhibitor of nitric oxide synthase, but NMMA did not reduce the decrease in transepithelial resistance. These results suggest that the greater adherence of alveolar macrophages to epithelial cells, the junctional change of the epithelial monolayer and the lysis of epithelial cells occur in this order in the LPS-exposed alveolar macrophage-SV40T2 coculture system, and the greater adherence of alveolar macrophages may play a role in LPS-induced inflammation in the rat lung.

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / cytology
  • Cell Adhesion / drug effects
  • Cell Communication / drug effects*
  • Cell Line
  • Epithelium / drug effects
  • Epithelium / pathology
  • Lipopolysaccharides / toxicity*
  • Lung / drug effects*
  • Lung / pathology*
  • Macrophages, Alveolar / drug effects*
  • Male
  • Plastics
  • Rats
  • Rats, Sprague-Dawley
  • Superoxide Dismutase / pharmacology
  • omega-N-Methylarginine / pharmacology


  • Lipopolysaccharides
  • Plastics
  • omega-N-Methylarginine
  • Superoxide Dismutase