Air Quality Guidelines Global Update 2005 - World Health ...

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AIR QUALITY GUIDELINES
Endothelial cell activation
Under the inputs provided by the series of inflammatory mediators listed above,
pulmonary endothelium is activated and actively participates in the process of
leukocyte adhesion and transmigration from the blood to pulmonary tissue. Leukocyte
recruitment to inflammatory sites is dictated by complementary adhesion
molecules expressed in leukocytes and endothelial membranes, which have their
expression and affinity increased by inflammatory mediators. By and large, adhesion
molecules belong to four families: selectins, immunoglobulin-like proteins,
integrins and mucin-like glycoproteins. The intensity and timing of expression
of these molecules provide important clues about the inflammatory process induced
by exposure to ozone.
Healthy non-smokers exposed to ozone for two hours had an increased
number of vessels exhibiting P-selectin 1½ hours later, despite the absence of
changes in pulmonary function or cell counts in BAL samples (63,94), indicating
that upregulation of P-selectin could signify an early inflammatory response
to ozone (such as margination and rolling of the neutrophils on the vessel wall)
prior to transendothelial migration. In a study comparing healthy volunteers to
asthmatics after exposure to 400 μg/m 3 for two hours, Stenfors et al. (95) reported
a significant increase of neutrophils in BAL fluid, as well as increased expression
of the endothelial adhesion molecules ICAM-1 and P-selectin 16 hours after exposure,
without evidence of increased intensity of such events in asthmatics.
Activation of pulmonary endothelium mediates neutrophil recruitment. Cultured
bovine pulmonary endothelial cells exposed to ozone at concentrations of
up to 2 mg/m 3 exhibited a concentration-dependent decrease in prostacyclin, a
potent vasodilator (96). In the same study it was shown that pulmonary hypoxic
vasoconstriction was augmented in dogs previously exposed to 2 mg/m 3 ozone.
Healthy volunteers exposed for two hours to a combination of concentrated ambient
particles (150 μg/m 3 ) and ozone (240 mg/m 3 ) showed significant brachial
artery vasoconstriction (97), indicating that short-term inhalation of fine particulate
air pollution and ozone at concentrations that occur in the urban environment
causes acute conduit artery vasoconstriction. Rats exposed for four
hours to inhalation of 1.6 mg/m 3 ozone plus 49 mg/m 3 EHC-93 (Ottawa particles)
showed higher mRNA levels of preproendothelin-1 and endothelin-converting
enzyme after two hours of exposure; this is consistent with the notion of
increased synthesis and conversion of the peptide endothelin-1 in lung endothelial
cells, indicating that lung endothelin system genes respond rapidly and transiently
to inhalation of urban pollutants (98). Non-smoking healthy adults exposed
to a combination of PM2.5 (147 mg/m 3 ) and ozone (240 mg/m 3 ) exhibited
an increase in diastolic blood pressure of 6 mmHg after two hours (99). Such
findings suggest that activation of pulmonary endothelium may take part in the
pathogenesis of ozone-induced cardiovascular events reported by recent epidemiological
studies.