Production of Reactive Oxygen Intermediates by Human Macrophages Exposed to Soot Particles and Asbestos Fibers and Increase in NF-kappa B p50/p105 mRNA

Abstract

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.

Increased mutant frequency by carbon black, but not quartz, in the lacZ and cII transgenes of muta™mouse lung epithelial cells

“…Further it is known that ROS can be generated through transition metals and other chemicals adhered to particles [Han et al, 2001;Sørensen et al, 2003]. Printex 90, however, contains very low amounts of such metals and chemicals [Oettinger et al, 1999;Borm et al, 2005]. Strand breaks are caused by numerous events such as damage by reactive molecules, cell cycle arrest, alkali labile sites, DNA repair and more.…”

“…Most exposures to airborne carbon black occur in the work place. Carbon black particles have large specific surface areas, and various chemicals such as polycyclic aromatic hydrocarbons (PAHs) [Borm et al, 2005] and metals can be adsorbed to the particle surface [Oettinger et al, 1999]. The presence of such carcinogenic compounds may contribute to the adverse health effects of carbon black exposure [Spurny, 1996].…”

Natural products as targeted modulators of the nuclear factor-κB pathway

“…However, descriptions of activity do not necessarily equate to potency and the following discussion will illustrate wide variations in cited levels of biological eOE ects. In addition, phenolics often possess antioxidant activity which could make them a nonspeci® c inhibitor of NF-j B by reducing reactive oxygen species, for example quercetin (Musonda & Chipman 1998) and resveratrol (Manna et al 2000a), which could otherwise activate NF-j B (Oettinger et al 1999). However, the evidence of a role for reactive oxygen species in NF-j B activation is limited to a few cell lines and only Black tea (Thea sinensis, Theaceae) polyphenols of thea¯avin derivatives and epigallocatechin-3-gallate (EGCG), were studied for their ability to suppress NFj B activation in LPS-stimulated RAW267.4 cells (Pan et al 2000b).…”

“…and resveratrol(Manna et al 2000a), which could otherwise activate NF-j B(Oettinger et al 1999). However, the evidence of a role for reactive oxygen species in NF-j B activation is limited to a few cell lines and only well characterised in lymphocytes (Ginn-Pease & Whisler 1998;Schoonbroodt & Piette 2000).…”

Spectroscopic investigation of PM2.5 collected at industrial, residential and traffic sites in Taif, Saudi Arabia

“…An EPR study of particles in tobacco smoke (Valavanidis et al, 2009) showed that there was synergistic effect between identified radicals and PM 2.5 particles illustrating the benefit of studying both radicals and PM 2.5 simultaneously. Several reports on the biological effects of combustion emissions are indicative of free-radical-mediated damage of the type that can be initiated by semiquinonetype radicals (Samet et al, 1995;Sagai et al, 2000;Oettinger et al, 1999). Recently, it has become evident that fine particulate matter has the ability to generate reactive oxygen species (ROS) (Pryor, 1997;Hellack et al, 2014).…”