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INSTILLATION OF COARSE ASH PARTICULATE MATTER AND LIPOPOLYSACCHARIDE PRODUCES A SYSTEMIC INFLAMMATORY RESPONSE IN MICE
Citation:
FINNERTY, K., J. CHOI, A. LAU, G. DAVIS-GORMAN, C. DIVEN, N. SEAVER, W. P. LINAK, M. WITTEN, AND P. F. MCDONAGH. INSTILLATION OF COARSE ASH PARTICULATE MATTER AND LIPOPOLYSACCHARIDE PRODUCES A SYSTEMIC INFLAMMATORY RESPONSE IN MICE. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. Taylor & Francis, Inc., Philadelphia, PA, Part A, 70(23):1957-1966, (2007).
Impact/Purpose:
Journal article
Description:
Coronary ischemic events increase significantly floowing a “bad air” day. Ambient particulate matter (PM10) is the pollutant most strongly associated with these events. PM10 causes inflammatory injury to the lower airways. It is not clear, however, if pulmonary inflation translates to a systemic response. Lipopolysaccharide (LPS) is a pro-inflammatory molecule often associated with the coarse fraction of PM. We hypothesize that PM>2.5 from coal plus LPS cause pulmonary inflation leading to a systemic inflammatory response. Mice were intratracheally instilled with saline, PM (200 micro grams), PM + LPS 10 micro grams, or PM + LPS 100 micro grams. Eighteen hours later histologic analysis was performed on lungs from each group. Pulmonary and systemic inflammation were accessed by measuring the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-a) and interleukin-6 (IL-6) in the pulmonary supernatant and plasma. In a follow up study the effects of LPS alone were assessed. Histologic analysis revealed a dose-dependent increase in pulmonary inflammation with all treatments. Pulmonary TNF-a and IL-6 both increased significantly with PM + LPS 100 treatment. Regarding plasma, TNF-a significantly increased in both PM + LPS 10 and PM + LPS 100 treatments. For plasma IL-6, all groups tended to increase with significant increase in the PM + LPS 100 group. The results of the follow-up study indicate that the responses to PM + LPS were not due to LPS alone. These results suggest that coarse coal fly ash PM >2.5 combined with LPS cause pulmonary and systemic inflammatory responses. The resulting low level systemic inflammation may contribute to the increased severity of ischemic heart disease observed immediately following a bad air day.
