Health Effects of Aerosols - Aerosols: Measurement, Dosimetry, and Health Effects - page 580

These investigators have developed a “stratiied oxidative stress model” to characterize both the
production of ROM by DEP and the mechanisms through which these ROM exert their effects on
inlammation and allergic response ([56]—the reader is referred to the extensive bibliography in this
review—selected references relevant to this section include [38,52,55,57-61]). The model is summa-
rized in Figure 23.14. These investigators demonstrated that low concentrations of redox-active PAHs

Oxy-PAHs
Present in PM
Produced by metabolic activation of PAHs in microsomes

Lipid peroxidation
of membranes
Cell death

Mitochondrial damage
Decreased membrane potential
disruption of internal structure

ROM

Antioxidant
response
element
in HO-1
promoter

Programmed cell
death (apoptosis)

Hemoxygenase 1( HO- 1)
sensitive marker of
oxidative stress
Manganese
superoxide
dismutase

Low oxidant stress
Antioxidant cytoprotection
anti-inflammatory(HO-1)
HO-1 effect not same for all cell types

Decreased ratio of
reduced/oxidized
glutathione

Higher levels of oxidant stress

Sensor/detector molecules
e.g., tyrosine kinases, GTP binding proteins

Activation of nuclear factor-kappa B

Miltogen-activated protein kinase cascade

Inflammation
Nonallergic
IgE-mediated
allergic

Transcriptional activation of genes
e.g., cytokine promotors
chemokine promotors
adhesion molecule promotors

FIGURE 23.14 Basic elements of “stratiied oxidative stress model” of Li et al. [56] (area enclosed in the gray
circle) and consequences of ROM that are not controlled by antioxidant defenses. Solid arrows represent the
pathways; dashed arrows identify feedback loops that perpetuate the adverse outcomes. ROM: reactive oxygen
metabolites. (Adapted from Li, N. et al., Environ. Health Perspect ., 111, 455, 2003; Li, N. et al., J. Immunol .,
169, 4531, 2002; Li, N. et al., J. Immunol ., 165, 3393, 2000; Li, N. et al., Inhal. Toxicol ., 14, 459, 2002; Nel,
A.E. et al., J. Allergy Clin. Immunol ., 102, 539, 1998; Hiura, T.S. et al., J. Immunol ., 163, 5582, 1999; Hiura,
T.S. et al., J. Immunol ., 165, 2703, 2000; Kumagai, Y. et al., Free Radic. Biol. Med ., 22, 479, 1997.)