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ROLE OF TOLL LIKE RECEPTORS ON PULMONARY INFLAMMATORY RESPONSES TO SIZE FRACTIONATED COMBUSTION AND AMBIENT AIR PARTICLES.
Citation:
GILMOUR, M.IAN I., M. J. DANIELS, E. BOYKIN, W. P. LINAK, AND R. B. DEVLIN. ROLE OF TOLL LIKE RECEPTORS ON PULMONARY INFLAMMATORY RESPONSES TO SIZE FRACTIONATED COMBUSTION AND AMBIENT AIR PARTICLES. . Presented at 45th Annual Society of Toxicology Meeting 2006, San Diego, CA, March 05 - 09, 2006.
Description:
C3H/HeJ mice feature a single point mutation in the Toll like receptor 4 gene which renders these animals resistant to a number of pro-inflammatory agents including lipopolysaccharide and ozone. This study compared pulmonary inflammatory responses in endotoxin resistant (C3H/HeJ) and susceptible mice (C3H/OUJ) after instillation of different size fractions (coarse, fine and ultrafine) of coal fly ash (CFA) or ambient air particles. No differences in pulmonary neutrophils were evident in either strain exposed to the various sizes of ambient PM. Coarse and fine ambient PM did however cause a greater increase in TNF-alpha release and albumin levels in the lung fluid of endotoxin sensitive mice, suggesting a requirement for Tlr-4 receptors in these responses. Coarse and fine CFA also caused a greater increase in PMNs, albumin and cytokine levels in the endotoxin sensitive mice, however no differences were observed after exposure to ultrafine CFA despite high level of responses. We conclude that soluble markers of inflammation and injury induced by coarse and fine particles are associated with a functional Tlr-4 pathway, whereas responses induced by ultrafine particles from combusted coal are not Tlr-4-dependent. PMN influx may be Tlr-4 dependent or independent depending on the stimulus. This abstract does not reflect EPA policy.