Effects of diesel exhaust particles (DEP), carbon black, and silica on macrophage responses to lipopolysaccharide: Evidence of DEP suppression of macrophage activity

The effects of diesel exhaust particle (DEP) exposure on alveolar macrophag e (AM) response to ex vivo and in vivo lipopolysaccharide (LPS) challenge w ere determined by monitoring LPS-stimulated production of interleukin-1 (IL -1) and tumor necrosis factor-alpha (TNF-alpha). The roles of the insoluble particulate and the organic compounds of DEP in altering pulmonary respons es were evaluated by comparing the DEP-induced pulmonary responses to those of carbon black (CB), a carbonaceous particle with few adsorbed organic co mpounds, or to silica, a known pneumotoxic dust. Male Sprague-Dawley rats w ere exposed to a single intratracheal dose (5 or 35 mg/kg body weight) of D EP, CB, or silica, or to saline vehicle. Ran were sacrificed 1, 3, or 7 d p ostexposure. To study the responsiveness to the bacterial product LPS, AM i solated from particle-exposed rats were challenged ex vivo with LPS (0.1 mu g/10(6) AM) and LPS-stimulated cytokine release was monitored. In addition , rats were exposed intratracheally to a single dose of DEP (5 mg/kg) and 3 d later exposed in vivo to 1 mg/kg LPS for 3 h prior to measurement of cyt okine production by AM. DEP exposure resulted in neutrophil infiltration an d elevated levels of albumin and lactate dehydrogenase (LDH) activity in th e bronchoalveolar lavage fluid; these responses were not substantially diff erent from those elicited by CB or silica exposure. AM from DEP-exposed rat s showed increased spontaneous production of IL-1, but not TNF-alpha, while the opposite was true for CB or silica. Upon ex vivo challenge with LPS, A M from DEP-exposed rats showed a significant decrease in the secretion of T NF-alpha and, to a lesser extent, IL-1, compared to the sum of the DEP and LPS effects. In contrast, AM from CB- or silica-exposed rats did not show t his decreased responsiveness to subsequent LPS challenge. This inhibitory a ction of DEP on LPS-stimulated AM production of IL-1 and TNF-alpha was furt her confirmed by the results obtained from rats exposed to both DEP and LPS in vivo. in summary, these results indicate that while DEP, CB, and silica all induce pulmonary inflammatory responses due to particle stimulation, o nly DEP suppress AM cytokine release in response to LPS stimulation. The co ntrasting cellular response with respect to DEP and CB exposures may be due to the presence of adsorbed organic compounds on DEP, which may contribute to the increased susceptibility of hosts to pulmonary infections after DEP exposure.