Adverse effects of wood smoke PM(2.5) exposure on macrophage functions

Inhal Toxicol. 2013 Feb;25(2):67-76. doi: 10.3109/08958378.2012.756086.

Abstract

Epidemiological studies have shown a correlation between chronic biomass smoke exposure and increased respiratory infection. Pulmonary macrophages are instrumental in both the innate and the adaptive immune responses to respiratory infection. In the present study, in vitro systems were utilized where alveolar macrophages (AM) and bone marrow-derived macrophages (BMdM) were exposed to concentrated wood smoke-derived particulate matter (WS-PM) and mice were exposed in vivo to either concentrated WS-PM or inhaled WS. In vivo studies demonstrated that WS-exposed mice inoculated with Streptococcus pneumoniae had a higher bacterial load 24 h post-exposure, and corresponding AM were found to have decreased lymphocyte activation activity. Additionally, while classic markers of inflammation (cellular infiltration, total protein, neutrophils) were not affected, there were changes in pulmonary macrophages populations, including significant decreases in macrophages expressing markers of activation in WS-exposed mice. The lymphocyte activation activity of WS-PM-exposed AM was significantly suppressed, but the phagocytic activity appeared unchanged. In an effort to determine a pathway for WS-induced suppression, RelB activation, assessed by nuclear translocation, was observed in AM exposed to either inhaled WS or instilled WS-PM. Finally, an analysis of WS-PM fractions determined the presence of 4-5 polycyclic aromatic hydrocarbons (PAHs), and preliminary work suggests a potential role for these PAHs to alter macrophage functions. These studies show a decreased ability of WS-exposed pulmonary macrophages to effectively mount a defense against infection, the effect lasts at least a week post-exposure, and appears to be mediated via RelB activation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / cytology
  • Cytochrome P-450 CYP1A1 / metabolism
  • Cytokines / metabolism
  • Macrophages / drug effects*
  • Macrophages / physiology
  • Mice
  • Mice, Inbred BALB C
  • Phagocytosis / drug effects
  • Pneumococcal Infections / microbiology
  • Polycyclic Aromatic Hydrocarbons / analysis
  • Polycyclic Aromatic Hydrocarbons / pharmacology
  • Receptors, Aryl Hydrocarbon / metabolism
  • Smoke / adverse effects*
  • Transcription Factor RelB / metabolism
  • Wood*

Substances

  • Cytokines
  • Polycyclic Aromatic Hydrocarbons
  • Receptors, Aryl Hydrocarbon
  • Relb protein, mouse
  • Smoke
  • Transcription Factor RelB
  • Cytochrome P-450 CYP1A1