title: Instillation of coarse ash particulate matter and lipopolysaccharide produces a systemic inflammatory response in mice.
abstract: Coronary ischemic events increase significantly following a "bad air" day. Ambient particulate matter (PM10) is the pollutant most strongly associated with these events. PM10 produces inflammatory injury to the lower airways. It is not clear, however, whether pulmonary inflammation translates to a systemic response. Lipopolysaccharide (LPS) is a proinflammatory molecule often associated with the coarse fraction of PM. It was hypothesized that PM>2.5 from coal plus LPS induce pulmonary inflammation leading to a systemic inflammatory response. Mice were intratracheally instilled with saline, PM (200 microg), PM + LPS10 (PM + 10 microg LPS), or PM + LPS100 (PM + 100 microg LPS). Eighteen hours later, histologic analysis was performed on lungs from each group. Pulmonary and systemic inflammation were assessed by measuring the proinflammatory cytokines tumor necrosis factor (TNF)-alpha and interleukin (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 elevation in pulmonary inflammation with all treatments. Pulmonary TNF-alpha and IL-6 both increased significantly with PM + LPS100 treatment. Regarding plasma, TNF-alpha significantly increased in both PM + LPS10 and PM + LPS100 treatments. For plasma IL-6, all groups tended to rise with a significant increase in the PM + LPS100 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 produced 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.
authors.affiliation: University of New Mexico School of Medicine, Albuquerque, New Mexico, USA.
authors.forename: Katie
authors.initials: K
authors.lastname: Finnerty
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Choi
authors.forename: Alexandria
authors.initials: A
authors.lastname: Lau
authors.forename: Grace
authors.initials: G
authors.lastname: Davis-Gorman
authors.forename: Conrad
authors.initials: C
authors.lastname: Diven
authors.forename: Norma
authors.initials: N
authors.lastname: Seaver
authors.forename: William P
authors.initials: WP
authors.lastname: Linak
authors.forename: Mark
authors.initials: M
authors.lastname: Witten
authors.forename: Paul F
authors.initials: PF
authors.lastname: McDonagh
mesh_terms: D000818:Animals; D003031:Coal / Q000009:adverse effects*; D004195:Disease Models, Animal; D004391:Dust / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood* / Q000378:metabolism; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000009:adverse effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D052638:Particulate Matter / Q000009:adverse effects* / Q000276:immunology; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood* / Q000378:metabolism
chemical_list: D003031:Coal; D004391:Dust; D015850:Interleukin-6; D008070:Lipopolysaccharides; D052638:Particulate Matter; D014409:Tumor Necrosis Factor-alpha