Health Effects of Aerosols - Aerosols: Measurement, Dosimetry, and Health Effects - page 582

the blood levels of ibrinogen, a procoagulant protein that is associated with acute inlammation
and blood clotting [94]. Humans exposed to the forest ires in Southeast Asia in 1997 [85,95]
showed evidence of increased pro-inlammatory cytokines and circulating neutrophils that were
related to the level of exposure. A recent study of controlled exposure of healthy and asthmatic
volunteers to concentrated ambient PM (CAP) showed increases in markers of systemic inlam-
mation [96]. Other data suggest that PM stimulation of sensory nerves in the epithelium of lung
airways (nonadrenergic/noncholinergic ibers and C-ibers) leads to airway inlammation through
peptidenergic transmitters (substance P, neurokinin A, and calcitonin-related gene product) and
that neural sensitivity is greater than that of airway epithelium to the effects of PM on inlamma-
tion [97] (see Table 23.6).
A considerable body of data has accumulated on the mechanism of the effects of diesel PM on
allergic inlammation. These have been summarized in detail by Nel et al. [57]. Table 23.7 sum-
marizes speciic indings that are related to the enhancement of IgE-mediated immune responses
in humans by diesel PM. The driving of the immune system toward IgE-mediated responses
could be reproduced with PAHs [98]. Of particular interest for the pathogenesis of new onset
allergic respiratory disease is the observation that diesel PM can induce sensitization to a neo-
antigen in persons already sensitized to an allergen that triggers IgE-induced allergic response
(Figure 23.15) [75]. In this study, the levels of the cytokine IL-4, which is a potent inducer of IgE
synthesis, were increased in the presence of antigen and diesel PM above those seen with antigen
alone. In contrast, the levels of INF-γ (interferon-γ), a Th-1 cytokine that relects the part of the
T-helper lymphocyte system that downregulates IL-4 production and stimulates cell-mediated
immunity, were not increased above those observed with antigen alone. While most of the stud-
ies related to PM immune enhancement have focused on diesel PM, other sources of PM, such
as ROFA, are also capable of the same type of immune enhancement [80,81,99]. These indings
are not surprising, if the underlying mechanism for this enhancement ultimately relates to the
production of ROM as discussed earlier.
TABLE 23.6
Summary of Effects of PM-Associated Transition Metals Derived from
Combustion of Coals from Three Different Sources in the United States
and from Gasoline and Diesel Exhaust
Oxidant generating capacity
Cu(II) > Fe(II) > Va(III) > Ni(II) > Co(II) ≅ Zn(II)
Each with different time kinetics and dose-response curves
Distribution of bioavailable Fe
Greatest in PM 2.5
PM 10-2.5 about 50% of PM 2.5
Oxidant potential
Coals: PM 1 > PM 2.5 > PM 10-2.5
PM 10-2.5 approximately 20%-100% as potent, dependent on source
Gasoline and diesel exhaust PM
Most oxidant production associated with transition metals (inhibited by desoxferamine (45%-97%)
Biological activity
Capacity of PM to produce IL-8 directly related to Fe content
Endotoxin content nondetectable in PM from three coal sources
Source: Aust, A.E. et al., Res. Rep. Health Eff. Inst ., 110, 1, 2002.