Inhalation of ultrafine particles alters blood leukocyte expression of adhesion molecules in humans

Abstract

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 approximately 25nm, geometric standard deviation approximately 1.6), for 2 hr, in three separate protocols: 10 microg/m3 at rest, 10 and 25 microg/m3 with exercise, and 50 microg/m3 with exercise. In a fourth protocol, subjects with asthma inhaled air and 10 microg/m3 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 microg/m3 UFPs reduced expression of CD11b on monocytes and eosinophils and CD54 on granulocytes. Particle exposure also reduced the percentage of CD4+ 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.

Figure 1

Changes in monocyte expression of CD54 (ICAM-1), UPDOSE protocol. In this and following figures, data are shown as mean ± SE changes from baseline. Nominal UFP exposure concentrations are shown in μg/m³. Exposure, p = 0.012.

Figure 2

Changes in leukocyte expression of adhesion molecules, UP50 protocol. (A) Monocyte expression of CD54, females. UFP × sex, p = 0.025. (B) Monocyte expression of CD54, males. UFP × sex, p = 0.025. (C) Monocyte expression of CD18. UFP, p = 0.0002. (D) PMN expression of CD18. UFP, p = 0.023.

Figure 3

Changes in leukocyte expression of adhesion molecules, UPASTHMA protocol. (A) Monocyte expression of CD11b. UFP, p = 0.029. (B) Eosinophil expression of CD11b. UFP, p = 0.015. (C) PMN expression of CD62L, females. UFP × sex, p = 0.011. (D) PMN expression of CD62L, males. UFP × sex, p = 0.011.

Figure 4

Changes in blood T-lymphocyte subsets. (A) UPDOSE protocol, percentage of CD25⁺ cells within the T-cell (CD3⁺) gate, females. UFP × sex, p = 0.0024. (B) UPDOSE protocol, CD3⁺CD25⁺ T cells, males. UFP × sex, p = 0.0024. (C) UP50 protocol, CD3⁺CD25⁺ T cells, all subjects. UFP × time, p = 0.085. (D) UPASTHMA protocol, CD4⁺ T cells, all subjects. UFP × time, p = 0.021.

Figure 5

Changes in percentage of blood leukocytes with exposure to UFPs. (A) UPDOSE protocol, monocytes, females. UFP × sex, p = 0.0015. (B) UPDOSE protocol, monocytes, males. UFP × sex, p = 0.0015. (C) UP50 protocol, eosinophils, females. UFP × time × sex, p = 0.01. (D) UP50 protocol, eosinophils, males. UFP × time × sex, p = 0.01.