Lung macrophage-epithelial cell interactions amplify particle-mediated cytokine release

Am J Respir Cell Mol Biol. 2002 Apr;26(4):499-505. doi: 10.1165/ajrcmb.26.4.4749.


Interactions between alveolar macrophages (AMs) and epithelial cells may promote inflammatory responses to air pollution particles. Normal rat AMs, the alveolar type II epithelial cell line RLE-6TN (RLE), or cocultures of both cell types were incubated with various particles (0-50 microg/ml) for 24 h, followed by assay of released TNF-alpha and MIP-2. The particles used included titanium dioxide (TiO2), alpha-quartz (SiO2), residual oil fly ash (ROFA), or urban air particles (UAP). For all particles, a dose-dependent increase in TNF-alpha and MIP-2 release was observed in AM+RLE co-cultures but not in RLE or AM monoculture. AM+RLE co-culture also synergistically enhanced basal levels of tumor necrosis factor (TNF)-alpha and macrophage inflammatory protein (MIP)-2. In contrast, when AMs were co-cultured with fibroblasts, basal and particle-induced TNF-alpha and MIP-2 were similar to levels found in AM monoculture. Particle uptake by AMs was similar in mono- or AM+RLE co-culture. Increased basal and particle-induced cytokine release were not observed when the AMs were physically separated from the RLE. This contact-dependent cytokine potentiation could not be blocked with anti-CD18/anti-CD54, arginine-glycine-aspartate (RGD) peptide, or heparin. We conclude that in vitro inflammatory responses to particles are amplified by contact-dependent interactions between AMs and epithelial cells. AM-epithelial co-culture may provide a useful model of in vivo particle effects.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Air Pollutants / adverse effects*
  • Animals
  • Cell Adhesion Molecules / metabolism
  • Cell Communication
  • Cells, Cultured
  • Chemokine CXCL2
  • Chemokines / metabolism
  • Coculture Techniques
  • Cytokines / metabolism*
  • Epithelial Cells / metabolism
  • Female
  • Lung / cytology*
  • Lung / metabolism*
  • Macrophages, Alveolar / cytology
  • Macrophages, Alveolar / drug effects
  • Macrophages, Alveolar / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Titanium / adverse effects
  • Tumor Necrosis Factor-alpha / metabolism


  • Air Pollutants
  • Cell Adhesion Molecules
  • Chemokine CXCL2
  • Chemokines
  • Cxcl2 protein, mouse
  • Cytokines
  • Tumor Necrosis Factor-alpha
  • titanium dioxide
  • Titanium