Citation:

Henriquez, A., W. Williams, S. Snow, Mette C. Schladweiler, C. Fisher, M. Hargrove, D. Alewel, C. Colonna, S. Gavett, C. Miller, AND U. Kodavanti. The Dynamicity of Acute Ozone-Induced Systemic Leukocyte Trafficking and Adrenal-Derived Stress Hormones. TOXICOLOGY. Elsevier Science Ltd, New York, NY, 458(152823):1, (2021). https://doi.org/10.1016/j.tox.2021.152823

Impact/Purpose:

We show a change in the pattern of circulating leukocyte trafficking over time during ozone exposure that follows early increases in adrenal-derived hormones, but not circulating cytokines. The increased expression of glucocorticoid responsive gene markers and inflammatory cytokines in the lung also follows glucocorticoid increases. We show that after a rapid increase of granulocytes in the circulation at 30 minutes of ozone exposure, it is followed by a general decline in all leukocyte populations over time. This suggests that they undergo initial egress and then rapid margination and extravasation, likely to the lung or other lymphoid organs.The temporal decline in circulating B and T lymphocytes during a 4 hour exposure period suggests that ozone-induced increases in epinephrine and corticosterone mediate redistribution of immune cells in response to lung injury.

Description:

Ozone exposure induces neuroendocrine stress response, which causes lymphopenia. It was hypothesized that ozone-induced increases in stress hormones will temporally follow changes in circulating granulocytes, monocytes- and lymphocyte subpopulations. The goal of this study was to chronicle the changes in circulating stress hormones, cytokines, and leukocyte trafficking during 4 h exposure to ozone. Male Wistar Kyoto rats were exposed to air or ozone (0.4 or 0.8 ppm) for 0.5, 1, 2, or 4 h. After each time point, circulating stress hormones, cytokines, and lung gene expression were assessed along with live and apoptotic granulocytes, monocytes (classical and non-classical), and lymphocytes (B, Th, and Tc) in blood, thymus, and spleen using flow cytometry. Circulating stress hormones began to increase at 1 h of ozone exposure. Lung expression of inflammatory cytokines (Cxcl2, Il6, and Hmox1) and glucocorticoid-responsive genes (Nr3c1, Fkbp5 and Tsc22d3) increased in both a time- and ozone concentration-dependent manner. Circulating granulocytes increased at 0.5 h of ozone exposure but tended to decrease at 2 and 4 h, suggesting a rapid egress and then margination to the lung. Classical monocytes decreased over 4 h of exposure periods (∼80 % at 0.8 ppm). B and Tc lymphocytes significantly decreased after ozone exposure at 2 and 4 h. Despite dynamic shifts in circulating immune cell populations, few differences were measured in serum cytokines. Ozone neither increased apoptotic cells nor altered thymus and spleen lymphocytes. The data show that ozone-induced increases in adrenal-derived stress hormones precede the dynamic migration of circulating immune cells, likely to the lung to mediate inflammation.

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