Production of reactive oxygen intermediates by human macrophages exposed to soot particles and asbestos fibers and increase in NF-kappa B p50/p105 mRNA

Alveolar macrophages (AM) play a decisive role in the immunologic defense system of the lung and in inflammatory pulmonary pathomechanisms. AM and blood monocytes (BM) were exposed to chrysotile B, soot FR 101, and Printex 90 (P 90). We evaluated the reactive oxygen intermediate (ROI) release of AM...

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Bibliographic Details
Published in:	Lung Vol. 177; no. 6; pp. 343 - 354
Main Authors:	Oettinger, R, Drumm, K, Knorst, M, Krinyak, P, Smolarski, R, Kienast, K
Format:	Journal Article
Language:	English
Published:	United States Springer Nature B.V 01-11-1999
Subjects:	Adult Aged Asbestos, Serpentine - administration & dosage Asbestos, Serpentine - adverse effects Bronchoalveolar Lavage Fluid - cytology Carbon - administration & dosage Carbon - adverse effects Cells, Cultured Dose-Response Relationship, Drug Female Gene Expression Regulation - drug effects Humans Luminescent Measurements Macrophages, Alveolar - drug effects Macrophages, Alveolar - metabolism Male Middle Aged Monocytes - drug effects Monocytes - metabolism NF-kappa B - drug effects NF-kappa B - genetics NF-kappa B - metabolism Reactive Oxygen Species - metabolism Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - drug effects RNA, Messenger - genetics RNA, Messenger - metabolism
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Summary:	Alveolar macrophages (AM) play a decisive role in the immunologic defense system of the lung and in inflammatory pulmonary pathomechanisms. AM and blood monocytes (BM) were exposed to chrysotile B, soot FR 101, and Printex 90 (P 90). We evaluated the reactive oxygen intermediate (ROI) release of AM and BM after particle exposure. ROI release was measured by chemiluminescence. Thirty-minute exposure caused a significant (up to 2.5-fold) increase in ROI release of AM (100 micrograms/10(6) cells) compared with control experiments (p < 0.01). Identical exposure conditions for BM resulted in a similar reaction pattern (maximum 2.2-fold increase in ROI release; p < 0.05). After a 90-min particle exposure at concentrations of 10 and 100 micrograms/10(6) cells, we investigated the steady-state level of p50/p105 mRNA encoding for the precursor protein of the p50 subunit of nuclear factor kappa B (NF-kappa B) by semiquantitative reverse transcription-polymerase chain reaction. One hundred micrograms Chrysotile B, FR 101, or P 90 induced a significant maximum 4.0-fold up-regulation of NF-kappa B gene expression in AM and a 3.3-fold up-regulation in BM (p < 0.05). The addition of superoxide dismutase (200 U/ml) to particle- and fiber-exposed macrophages resulted in inhibition of ROI release and a decrease in NF-kappa B mRNA expression (70%). NF-kappa B is an important transcription factor involved in the regulation of numerous genes (e.g., for inflammatory cytokines, and cytokine receptors). These cytokines are supposed to be involved in inflammatory pathomechanisms in bronchial epithelial cells, which result, for example, in chronic obstructive pulmonary disease. Our results suggest that particle-induced ROI release is associated with an increase in NF-kappa B (p50/p105) mRNA steady-state level.
ISSN:	0341-2040 1432-1750
DOI:	10.1007/pl00007652