Academic journal article Environmental Health Perspectives

Inhalation of Ultrafine Particles Alters Blood Leukocyte Expression of Adhesion Molecules in Humans

Academic journal article Environmental Health Perspectives

Inhalation of Ultrafine Particles Alters Blood Leukocyte Expression of Adhesion Molecules in Humans

Article excerpt

Ultrafine particles (UFPs; aerodynamic diameter < 100 nm) may contribute to the respiratory and cardiovascular morbidity and mortality associated with particulate air pollution. We tested the hypothesis that inhalation of carbon UFPs has vascular effects in healthy and asthmatic subjects, detectable as alterations in blood leukocyte expression of adhesion molecules. Healthy subjects inhaled filtered air and freshly generated elemental carbon particles (count median diameter 25 nm, geometric standard deviation ~ 1.6), for 2 hr, in three separate protocols: 10 [micro]g/[m.sup.3] at rest, 10 and 25 [micro]g/[m.sup.3] with exercise, and 50 [micro]g/[m.sup.3] with exercise. In a fourth protocol, subjects with asthma inhaled air and 10 [micro]g/[m.sup.3] UFPs with exercise. Peripheral venous blood was obtained before and at intervals after exposure, and leukocyte expression of surface markers was quantitated using multiparameter flow cytometry. In healthy subjects, particle exposure with exercise reduced expression of adhesion molecules CD54 and CD18 on monocytes and CD18 and CD49d on granulocytes. There were also concentration-related reductions in blood monocytes, basophils, and eosinophils and increased lymphocyte expression of the activation marker CD25. In subjects with asthma, exposure with exercise to 10 [micro]g/[m.sup.3] UFPs reduced expression of CD 11 b on monocytes and eosinophils and CD54 on granulocytes. Particle exposure also reduced the percentage of CD[4.sup.+] T cells, basophils, and eosinophils. Inhalation of elemental carbon UFPs alters peripheral blood leukocyte distribution and expression of adhesion molecules, in a pattern consistent with increased retention of leukocytes in the pulmonary vascular bed. Key words: blood leukocytes, human, monocytes, ultrafine particles. Environ Health Perspect 114:51-58 (2006). doi:10.1289/ehp.7962 available via http://dx.doi.org/[Online 20 September 2005]

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Exposure to particulate matter (PM) air pollution is associated with increased respiratory and cardiovascular morbidity and mortality (Peters et al. 2000, 2001a; Pope et al. 2004). Plausible mechanisms explaining the cardiovascular effects of particle exposure have not been clearly defined (Utell et al. 2002). However, recent studies provide evidence that PM exposure is associated with systemic inflammation and changes in vascular function that have been implicated in the pathophysiology of cardiovascular disease, providing clues to possible mechanisms. PM exposure has been associated with increased systolic blood pressure (Ibald-Mulli et al. 2001), plasma viscosity (Peters et al. 1997a), C-reactive protein (Peters et al. 2001b), fibrinogen (Pekkanen et al. 2000), and release of leukocytes from the bone marrow (Mukae et al. 2001; Tan et al. 2000). Increases in ambient concentrations of PM were associated with increased blood leukocyte and platelet counts, as well as fibrinogen (Schwartz 2001). Brook et al. (2002) found evidence for systemic vasoconstriction in resting human subjects exposed to concentrated ambient air particles and ozone.

Ultrafine particles (UFPs), defined as particles with a diameter < 100 nm, have been hypothesized as contributors to cardiovascular effects of PM (Seaton et al. 1995) because, compared with fine particles at similar mass concentrations, they have greater pulmonary deposition efficiency (Chalupa et al. 2004; Daigle et al. 2003), induce more pulmonary inflammation (Li et al. 1999; Oberdorster et al. 1995), have enhanced oxidant capacity (Brown et al. 2001; Li et al. 2003), have a higher propensity to penetrate the epithelium and reach interstitial sites (Stearns et al. 1994), and may even enter the systemic circulation in humans (Nemmar et al. 2002; Oberdorster et al. 2002).

Relatively few epidemiologic studies have examined the health effects of UFP exposure because most ambient air monitoring measures particle mass, and there is relatively poor correlation between particle mass (dominated by fine particles) and particle number (dominated by UFPs). …

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