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PI: J.T. Zelikoff; Co-I: M. Cohen; Consultants: L.C. Chen, R.B. Schlesinger.
>These studies will correlate the physicochemical
attributes of ambient PM with its in vivo immunotoxicity,
so as to identify and characterize the role of particle size
(i.e., fine/ultrafine), form (i.e., soluble vs. insoluble),
and constitutive transition metals in the exacerbation of an
ongoing S. pneumoniae infection. Previous investigations
in this laboratory have demonstrated that a single 5 hr inhalation
exposure of Streptococcus pneumoniae-infected rats to
concentrated ambient PM2.5 from New York City (NYC) air altered
both pulmonary and systemic immunity, as well as exacerbated
the infection process, in a time-post-exposure-dependent manner.
Bacterial clearance will be used to evaluate the role of the
various physico-chemical characteristics of PM upon disease exacerbation.
Rats will be exposed nose-only for a single 5 hr exposure to
atmospheres containing differentially-sized PM fractions (i.e.,
fine [0.2 -2.5 µm] and ultrafine [< 0.2 µm]).
We will subsequently analyze the role of solubility and composition
in PM-induced immunotoxicity, focussing upon the size fraction
that demonstrated the most dramatic effects upon intrapulmonary
bacterial killing. Samples of ambient NYC PM will be size-separated
and collected onto Teflon filters using a MOUDI impactor. The
PM will be recovered, and the sized particles will be extracted
to generate soluble and insoluble metal-bearing subfractions
for use in analytical assessments.
To determine the role that PM-associated transition metal
solubility and concentration might play in bringing about the observed changes
in host immunocompetence, infected rats will be exposed to artificially-generated
atmospheres containing soluble/insoluble forms of the individual metals found
at the highest concentrations in the immunoreactive fraction. Similar studies
will then employ mixtures of soluble/insoluble forms of more than one metal,
so as to ascertain whether the observed immunosuppression in PM-exposed hosts
is dependent, in part, upon any synergistic/additive interactions among the
transition metals present.
The results should provide necessary information as to characteristics
of PM responsible for the observed effects upon host immunocompetence, and
help to clarify the role that size plays in host pulmonary immunmodulation.
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