Effects of diesel exhaust particles on human alveolar macrophage ability to secrete inflammatory mediators in response to lipopolysaccharide

• Published in: Toxicology (Amsterdam) 2006-08, Vol.20 (5), p.614-624
• Main Authors: Mundandhara, Sailaja D., Becker, Susanne, Madden, Michael C.
• Format: Article
• Language: English
• Subjects: Cell Survival - drug effects; Diesel exhaust particles; Dinoprostone - secretion; Female; Human alveolar macrophages; Humans; Immune function; In Vitro Techniques; Inflammation Mediators - metabolism; Interleukin-8 - secretion; Lipopolysaccharide (LPS); Lipopolysaccharides - toxicity; Macrophages, Alveolar - drug effects; Macrophages, Alveolar - secretion; Male; Teichoic Acids - toxicity; Tumor Necrosis Factor-alpha - secretion; Vehicle Emissions - toxicity
• ISSN: 0887-2333; 0300-483X; 1879-3177
• DOI: 10.1016/j.tiv.2005.10.018

Ambient particulate matter (PM) has been shown to be associated with mortality and morbidity. Diesel exhaust particles (DEP) contribute to ambient PM. Alveolar macrophages (AM) are important targets for PM effects in the lung. The effects of DEP exposure on human AM response to lipopolysachharide (LPS; from gram-negative bacteria) challenge in vitro were determined by monitoring the production of interleukin 8 (IL-8), tumor necrosis factor-α (TNF-α) and prostaglandin E 2 (PGE 2). The roles of organic compounds and carbonaceous core of DEP in response to LPS were evaluated by comparing the DEPs effect to that of carbon black (CB), a carbonaceous particle with few adsorbed organic compounds. AMs were exposed in vitro to Standard Reference Material (SRM) DEP 2975, SRM DEP 1650, SRM 1975 (a dichloromethane extract of SRM DEP 2975) and CB particles for 24 h. DEPs induced a decreased secretion of IL-8, TNF-α and PGE 2 in response to a subsequent LPS stimulation. DEPs also show suppressive effect on the release of inflammatory mediators when stimulated with lipoteichoic acid, a product of gram positive bacteria. In summary, in vitro exposure of human AM to DEPs significantly suppress AM responsiveness to gram-negative and positive bacterial products, which may be a contributing factor to the impairment of pulmonary defense.