Interaction of alveolar macrophages and airway epithelial cells following exposure to particulate matter produces mediators that stimulate the bone marrow

Am J Respir Cell Mol Biol. 2002 Jul;27(1):34-41. doi: 10.1165/ajrcmb.27.1.4787.


Exposure to ambient air pollution particles with a diameter of < 10 microm (PM(10)) has been associated with increased cardiopulmonary morbidity and mortality. We postulate that these adverse health effects are related to proinflammatory mediators produced in the lung and released into the circulation where they initiate a systemic inflammatory response. The present study was designed to determine if alveolar macrophages (AMs) and primary human bronchial epithelial cells (HBECs) interact to amplify the production of certain cytokines when exposed to ambient PM(10) (EHC-93). Candidate cytokines were measured at the mRNA level using a RNase protection assay and at the protein level by enzyme-linked immunosorbent assay (ELISA). When AM/HBEC cocultures were exposed to 100 microg/ml of PM(10), levels of tumor necrosis factor (TNF)-alpha, granulocyte macrophage colony stimulating factor (GM-CSF), interleukin (IL)-1beta, IL-6, leukemia inhibitory factor (LIF), oncostatin M (OSM), and IL-8 mRNA increased within 2 h (P < 0.05) and 8 h following exposure compared with control cells. GM-CSF mRNA expression was more rapidly induced in cocultured cells compared with HBECs or AMs alone. The concentrations of TNF-alpha, GM-CSF, IL-1beta, IL-6, and IL-8 in the cocultured supernatants collected after 24 h PM(10) exposure increased significantly compared with control cells. There was a significant synergistic effect between AMs and HBECs in the production of GM-CSF and of IL-6 (P < 0.05). Instillation of supernatants from HBECs cultured with PM(10) into lungs of rabbits failed to increase circulating band cell counts or stimulate the bone marrow. However, those from AM/HBEC cocultures exposed to PM(10) increased circulating band cell counts (P < 0.05) and shortened the transit time of polymorphonuclear leukocytes (PMNs) through the bone marrow compared with control co-cultures (P < 0.01). These results suggest that the interaction between AMs and HBECs during PM(10) exposure contributes to the production of mediators that induce a systemic inflammatory response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Air Pollutants / adverse effects*
  • Animals
  • Bone Marrow / drug effects
  • Bone Marrow / physiology*
  • Bronchi / cytology
  • Cell Communication / drug effects
  • Cell Communication / physiology
  • Cells, Cultured
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Cytokines / pharmacology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism*
  • Epithelial Cells / physiology
  • Humans
  • Macrophages, Alveolar / drug effects
  • Macrophages, Alveolar / metabolism
  • Macrophages, Alveolar / physiology*
  • Neutrophils / cytology
  • Neutrophils / drug effects
  • Neutrophils / physiology
  • Particle Size
  • RNA, Messenger / biosynthesis
  • Rabbits


  • Air Pollutants
  • Cytokines
  • RNA, Messenger