Endotoxin and polycyclic aromatic hydrocarbons in ambient fine particulate matter from Fresno, California initiate human monocyte inflammatory responses mediated by reactive oxygen species

Toxicol In Vitro. 2010 Oct;24(7):1993-2002. doi: 10.1016/j.tiv.2010.08.017. Epub 2010 Aug 27.

Abstract

In urban areas, a correlation between exposure to particulate matter (PM) from air pollution and increased cardiovascular morbidity and mortality has been observed. Components of PM include bacterial contaminants, transition metals, salts, polycyclic aromatic hydrocarbons (PAH), and carbonaceous material, which could interact with various cell types to produce systemic responses when inhaled. We examined the effects of PM collected from Fresno, California on activation of human monocytes and their interaction with vascular endothelium, a key event in atherogenesis. PM exposure increased cytokine expression and secretion from monocytes and enhanced monocyte adhesion to human aortic endothelial cells, both of which were attenuated by neutralizing endotoxin. PM also increased monocyte CYP1a1 expression, and inhibition of the aryl hydrocarbon receptor reduced the CYP1a1 and inflammatory responses. PM-treated monocytes accumulated intracellular reactive oxygen species (ROS), and antioxidants attenuated inflammatory and xenobiotic responses. Finally, supernatants from PM-treated pulmonary microvascular endothelial cells induced monocyte inflammatory responses that were not a consequence of endotoxin transfer. These results suggest that certain components of urban PM, namely endotoxin and PAH, activate circulating monocytes directly or indirectly by first stimulating other cells such as pulmonary endothelial cells, providing several mechanisms by which PM inhalation could induce pulmonary and/or systemic inflammation.

Publication types

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

MeSH terms

  • Air Pollutants / adverse effects*
  • Air Pollutants / chemistry
  • Air Pollution / adverse effects
  • Aorta / cytology
  • Aorta / drug effects
  • California
  • Cell Adhesion / drug effects
  • Cell Line, Tumor
  • Cells, Cultured
  • Cytokines / drug effects
  • Cytokines / metabolism
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Endotoxins / isolation & purification
  • Endotoxins / toxicity*
  • Humans
  • Monocytes / drug effects*
  • Monocytes / metabolism
  • Particulate Matter / chemistry
  • Particulate Matter / toxicity
  • Polycyclic Aromatic Hydrocarbons / isolation & purification
  • Polycyclic Aromatic Hydrocarbons / toxicity*
  • Reactive Oxygen Species / metabolism

Substances

  • Air Pollutants
  • Cytokines
  • Endotoxins
  • Particulate Matter
  • Polycyclic Aromatic Hydrocarbons
  • Reactive Oxygen Species