title: Pathological and immunological effects of respirable coal fly ash in male Wistar rats.
abstract: In this study the effects of inhalatory exposure to coal fly ash on lung pathology and the immune system in rats were examined. Rats were exposed to 0, 10, 30, or 100 mg/m(3) coal fly ash (6 h/day, 5 days/wk) for 4 wk, or to 0 and 100 mg/m(3) for 1 wk, and for 1 wk followed by a recovery in clean air of 3 wk. A concentration-related increase in lung weight was found starting from 30 mg/m(3) coal fly ash. After exposure to 100 mg/m(3), a time-related deposition of free particles in the lungs was observed as well as a time-related number of coal fly ash particles phagocytized in alveolar macrophages. Histological examination revealed increased cellularity in alveolar septa, consisting mainly of mononuclear cell infiltrate, proliferated type II cells, and a slight fibrotic reaction. After a recovery period of 3 wk the histological picture was identical to that after 1 wk of exposure, indicating no significant recovery. No toxicological significant changes were found in the hematological, clinical chemistry, or urine parameters. Effects both on nonspecific defense mechanisms and on specific immune responses were noted. With regard to the immune function in the draining lymph nodes of the lung, a significantly increased number of both T and B lymphocytes was observed. The ratio of both cell types was not changed in either of the groups. In serum of exposed rats a significant increase of up to 150% of the immunoglobulin A (IgA) content was found. The number and phagocytic capacity of macrophages were significantly increased, while the killing of Listeria bacteria per cell ex vivo/in vitro remained unchanged. Natural killer (NK) activity in pulmonary cell suspensions was slightly stimulated in rats exposed for 4 wk to 10 and 30 mg/m(3), whereas an exposure to 100 mg/m(3) resulted in a slight decrease; however, both changes were not significant. In conclusion, the alterations in lung histopathology and immunity, observed in a dose and exposure time relation at concentrations up to and including 100 mg/m(3) coal fly ash, may be considered an adverse response of the host to inhalation of particulate matter. Whether these observed alterations may effect the host resistance must be learned from infection studies.
authors.affiliation: Laboratory for Pathology and Immunobiology, National Institute of Public Health and the Environment, P.O. Box 1, 3720 BA Bilthoven, The Netherlands. j.dormans@rivm.nl
authors.forename: J A
authors.initials: JA
authors.lastname: Dormans
authors.forename: P A
authors.initials: PA
authors.lastname: Steerenberg
authors.forename: J H
authors.initials: JH
authors.lastname: Arts
authors.forename: L
authors.initials: L
authors.lastname: van Bree
authors.forename: A
authors.initials: A
authors.lastname: de Klerk
authors.forename: A P
authors.initials: AP
authors.lastname: Verlaan
authors.forename: J P
authors.initials: JP
authors.lastname: Bruijntjes
authors.forename: P
authors.initials: P
authors.lastname: Beekhof
authors.forename: D
authors.initials: D
authors.lastname: van Soolingen
authors.forename: H
authors.initials: H
authors.lastname: van Loveren
mesh_terms: D000395:Air Pollutants, Occupational / Q000276:immunology* / Q000633:toxicity*; D000818:Animals; D001273:Atmosphere Exposure Chambers; D001402:B-Lymphocytes / Q000187:drug effects; D001770:Blood Bactericidal Activity; D001774:Blood Chemical Analysis; D001835:Body Weight / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002244:Carbon / Q000276:immunology* / Q000633:toxicity*; D003031:Coal / Q000633:toxicity*; D060729:Coal Ash; D007136:Immunoglobulins / Q000096:biosynthesis / Q000276:immunology; D007220:Industrial Waste; D019570:Inhalation Exposure / Q000009:adverse effects*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008168:Lung / Q000473:pathology; D008297:Male; D009426:Netherlands; D009929:Organ Size / Q000187:drug effects; D052638:Particulate Matter; D010587:Phagocytosis / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018570:Risk Assessment; D013601:T-Lymphocytes / Q000187:drug effects
chemical_list: D000395:Air Pollutants, Occupational; D003031:Coal; D060729:Coal Ash; D007136:Immunoglobulins; D007220:Industrial Waste; D052638:Particulate Matter; D002244:Carbon